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Sample records for accelerated mouse prone

  1. Systematic Analysis of Long Noncoding RNAs in the Senescence-accelerated Mouse Prone 8 Brain Using RNA Sequencing

    PubMed Central

    Zhang, Shuai; Qin, Chunxia; Cao, Guoqiong; Xin, Wenfeng; Feng, Chengqiang; Zhang, Wensheng

    2016-01-01

    Long noncoding RNAs (lncRNAs) may play an important role in Alzheimer's disease (AD) pathogenesis. However, despite considerable research in this area, the comprehensive and systematic understanding of lncRNAs in AD is still limited. The emergence of RNA sequencing provides a predictor and has incomparable advantage compared with other methods, including microarray. In this study, we identified lncRNAs in a 7-month-old mouse brain through deep RNA sequencing using the senescence-accelerated mouse prone 8 (SAMP8) and senescence-accelerated mouse resistant 1 (SAMR1) models. A total of 599,985,802 clean reads and 23,334 lncRNA transcripts were obtained. Then, we identified 97 significantly upregulated and 114 significantly downregulated lncRNA transcripts from all cases in SAMP8 mice relative to SAMR1 mice. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these significantly dysregulated lncRNAs were involved in regulating the development of AD from various angles, such as nerve growth factor term (GO: 1990089), mitogen-activated protein kinase signaling pathway, and AD pathway. Furthermore, the most probable AD-associated lncRNAs were predicted and listed in detail. Our study provided the systematic dissection of lncRNA profiling in SAMP8 mouse brain and accelerated the development of lncRNA biomarkers in AD. These attracting biomarkers could provide significant insights into AD therapy in the future. PMID:27483026

  2. L-Lysine suppresses myofibrillar protein degradation and autophagy in skeletal muscles of senescence-accelerated mouse prone 8.

    PubMed

    Sato, Tomonori; Ito, Yoshiaki; Nagasawa, Takashi

    2017-02-01

    Sarcopenia is a condition of the loss of muscle mass that is associated with aging and that increases the risk for bedridden state, thereby warranting studies of interventions that attenuate sarcopenia. Here the effects of 2-month dietary L-lysine (Lys) supplementation (1.5-3.0 %) on myofibrillar protein degradation and major proteolytic systems were investigated in senescence-accelerated mouse prone 8 (SAMP8). At 36 weeks of age, skeletal muscle and lean body mass was reduced in SAMP8 when compared with control senescence-accelerated mouse resistant 1 (SAMR1). The myofibrillar protein degradation, which was evaluated by the release of 3-methylhistidine, was stimulated in SAMP8, and the autophagy activity, which was evaluated by light chain 3-II, was stimulated in the skeletal muscle of SAMP8. The activation of ubiquitin-proteasome system was not observed in the muscles of SAMP8. However, myofibrillar protein degradation and autophagic activity in skeletal muscles of SAMP8 were suppressed by dietary intake of 3.0 % Lys. The present data indicate that myofibrillar protein degradation by bulk autophagy is stimulated in the skeletal muscles of SAMP8 and that dietary Lys supplementation attenuates sarcopenia in SAMP8 by suppressing autophagic proteolysis.

  3. Defects in subventricular zone pigmented epithelium-derived factor niche signaling in the senescence-accelerated mouse prone-8.

    PubMed

    Castro-Garcia, Paola; Díaz-Moreno, María; Gil-Gas, Carmen; Fernández-Gómez, Francisco J; Honrubia-Gómez, Paloma; Álvarez-Simón, Carmen Belén; Sánchez-Sánchez, Francisco; Cano, Juan Carlos Castillo; Almeida, Francisco; Blanco, Vicente; Jordán, Joaquín; Mira, Helena; Ramírez-Castillejo, Carmen

    2015-04-01

    We studied potential changes in the subventricular zone (SVZ) stem cell niche of the senescence-accelerated mouse prone-8 (SAM-P8) aging model. Bromodeoxyuridine (BrdU) assays with longtime survival revealed a lower number of label-retaining stem cells in the SAM-P8 SVZ compared with the SAM-Resistant 1 (SAM-R1) control strain. We also found that in SAM-P8 niche signaling is attenuated and the stem cell pool is less responsive to the self-renewal niche factor pigmented epithelium-derived factor (PEDF). Protein analysis demonstrated stable amounts of the PEDF ligand in the SAM-P8 SVZ niche; however, SAM-P8 stem cells present a significant expression decrease of patatin-like phospholipase domain containing 2, a receptor for PEDF (PNPLA2-PEDF) receptor, but not of laminin receptor (LR), a receptor for PEDF (LR-PEDF) receptor. We observed changes in self-renewal related genes (hairy and enhancer of split 1 (Hes1), hairy and enhancer of split 1 (Hes5), Sox2] and report that although these genes are down-regulated in SAM-P8, differentiation genes (Pax6) are up-regulated and neurogenesis is increased. Finally, sheltering mammalian telomere complexes might be also involved given a down-regulation of telomeric repeat binding factor 1 (Terf1) expression was observed in SAM-P8 at young age periods. Differences between these 2 models, SAM-P8 and SAM-R1 controls, have been previously detected at more advanced ages. We now describe alterations in the PEDF signaling pathway and stem cell self-renewal at a very young age, which could be involved in the premature senescence observed in the SAM-P8 model.

  4. LW-AFC Effects on N-glycan Profile in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer’s Disease

    PubMed Central

    Wang, Jianhui; Cheng, Xiaorui; Zeng, Ju; Yuan, Jiangbei; Wang, Zhongfu; Zhou, Wenxia; Zhang, Yongxiang

    2017-01-01

    Glycosylation is one of the most common eukaryotic post-translational modifications, and aberrant glycosylation has been linked to many diseases. However, glycosylation and glycome analysis is a significantly challenging task. Although several lines of evidence have indicated that protein glycosylation is defective in Alzheimer’s disease (AD), only a few studies have focused on AD glycomics. The etiology of AD is unclear and there are no effective disease-modifying treatments for AD. In this study, we found that the object recognition memory, passive avoidance, and spatial learning and memory of senescence-accelerated mouse prone 8 (SAMP8) strain, an AD animal model, were deficient, and LW-AFC, which was prepared from the traditional Chinese medicine prescription Liuwei Dihuang decoction, showed beneficial effects on the deterioration of cognitive capability in SAMP8 mice. Forty-three and 56 N-glycan were identified in the cerebral cortex and serum of SAMP8 mice, respectively. The N-glycan profile in SAMP8 mice was significantly different from that of senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. Treatment with LW-AFC modulated the abundance of 21 and 6 N-glycan in the cerebral cortex and serum of SAMP8 mice, respectively. The abundance of (Hex)3(HexNAc)5(Fuc)1(Neu5Ac)1 and (Hex)2(HexNAc)4 decreased in the cerebral cortex and serum of SAMP8 mice compared with SAMR1 mice, decreases that were significantly correlated with learning and memory measures. The administration of LW-AFC could reverse or increase these levels in SAMP8 mice. These results indicated that the effects of LW-AFC on cognitive impairments in SAMP8 mice might be through modulation of N-glycan patterns, and LW-AFC may be a potential anti-AD agent. PMID:28203484

  5. Age-Related Alterations in the Metabolic Profile in the Hippocampus of the Senescence-Accelerated Mouse Prone 8: A Spontaneous Alzheimer's Disease Mouse Model

    PubMed Central

    Wang, Hualong; Lian, Kaoqi; Han, Bing; Wang, Yanyong; Kuo, Sheng-Han; Geng, Yuan; Qiang, Jing; Sun, Meiyu; Wang, Mingwei

    2015-01-01

    Alzheimer's disease (AD), the most common age-dependent neurodegenerative disorder, produces a progressive decline in cognitive function. The metabolic mechanism of AD has emerged in recent years. In this study, we used multivariate analyses of gas chromatography-mass spectrometry measurements to determine that learning and retention-related metabolic profiles are altered during aging in the hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in 17 metabolites were detected in mature and aged mice compared to young mice (13 decreased and 4 increased metabolites), including metabolites related to dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid, and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine, aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid), and other altered metabolites (increased N-acetyl-aspartic acid and decreased pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these alterations indicated that the metabolic mechanisms of age-related cognitive impairment in SAMP8 mice were related to multiple pathways and networks. Lipid metabolism, especially cholesterol metabolism, appears to play a distinct role in the hippocampus in AD. PMID:24284365

  6. The behavioral, pathological and therapeutic features of the senescence-accelerated mouse prone 8 strain as an Alzheimer's disease animal model.

    PubMed

    Cheng, Xiao-rui; Zhou, Wen-xia; Zhang, Yong-xiang

    2014-01-01

    Alzheimer's disease (AD) is a widespread and devastating progressive neurodegenerative disease. Disease-modifying treatments remain beyond reach, and the etiology of the disease is uncertain. Animal model are essential for identifying disease mechanisms and developing effective therapeutic strategies. Research on AD is currently being carried out in rodent models. The most common transgenic mouse model mimics familial AD, which accounts for a small percentage of cases. The senescence-accelerated mouse prone 8 (SAMP8) strain is a spontaneous animal model of accelerated aging. Many studies indicate that SAMP8 mice harbor the behavioral and histopathological signatures of AD, namely AD-like cognitive and behavioral alterations, neuropathological phenotypes (neuron and dendrite spine loss, spongiosis, gliosis and cholinergic deficits in the forebrain), β-amyloid deposits resembling senile plaques, and aberrant hyperphosphorylation of Tau-like neurofibrillary tangles. SAMP8 mice are useful in the development of novel therapies, and many pharmacological agents and approaches are effective in SAMP8 mice. SAMP8 mice are considered a robust model for exploring the etiopathogenesis of sporadic AD and a plausible experimental model for developing preventative and therapeutic treatments for late-onset/age-related AD, which accounts for the vast majority of cases.

  7. Neuroprotective effect of the Chinese medicine Tiantai No. 1 and its molecular mechanism in the senescence-accelerated mouse prone 8

    PubMed Central

    Li, Ying-hong; Wang, Xu-sheng; Chen, Xiao-lin; Jin, Yu; Chen, Hong-bo; Jia, Xiu-qin; Zhang, Yong-feng; Wu, Zheng-zhi

    2017-01-01

    Tiantai No. 1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No. 1 intragastrically to senescence-accelerated mouse prone 8 (SAMP8) mice (a model of Alzheimer's disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer's disease-related proteins in the brain. Tiantai No. 1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No. 1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No. 1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No. 1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No. 1 is neuroprotective in the SAMP8 mouse model of Alzheimer's disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

  8. Effect of vitamin K2 on the development of stress-induced osteopenia in a growing senescence-accelerated mouse prone 6 strain

    PubMed Central

    KATSUYAMA, HIRONOBU; FUSHIMI, SHIGEKO; YAMANE, KUNIKAZU; WATANABE, YOKO; SHIMOYA, KOICHIRO; OKUYAMA, TOSHIKO; KATSUYAMA, MIDORI; SAIJOH, KIYOFUMI; TOMITA, MASAFUMI

    2015-01-01

    Vitamin K2 (VK2) has been used as a therapeutic agent for osteoporosis, since it has been suggested to be able to reduce the frequency of fractures by improving bone quality; however, bone turnover is strictly regulated by various cytokines and hormones. In the present study, the effect of menaquinone-4 (MK-4) on bone turnover was investigated using the senescence-accelerated mouse prone 6 (SAMP6) strain. Since water-immersion restraint stress (WRS) causes a significant decrease in bone mineral density (BMD), WRS was used as the bone resorption model in the SAMP6 strain. Six-week-old SAMP6 male mice were divided into the following three groups: Control, WRS and WRS + MK-4. WRS was performed for 6 h per day, 5 times a week, for 4 weeks. Following WRS, MK-4 (30 mg/kg) was injected subcutaneously 3 times a week for 4 weeks. No growth retardation was observed in the WRS groups as compared with the control group. In the WRS groups, the BMD was significantly lower than that in the control group. The levels of bone formation and resorption markers were increased in the WRS groups, indicating that WRS reduced the BMD by promoting high bone turnover. A bone histomorphometrical examination showed that the trabecular (Tb) bone mass in the secondary spongiosa at the distal femur was significantly reduced in the WRS mice, and this reduction was abrogated by MK-4 treatment. Specifically, the Tb bone reduction was caused by the activation of osteoclasts (Ocs), and Oc activity was suppressed by MK-4. The number of osteoblasts and the mineral apposition rate were significantly increased in the WRS and WRS + MK-4 mice, suggesting that WRS triggered a significantly higher mineral apposition rate. These results indicate that MK-4 can induce recovery from the bone mineral loss caused by WRS treatment. Further studies are required to clarify the association between bone quality and MK-4. PMID:26622403

  9. Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse

    PubMed Central

    Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg; Kumagai, Kazuyoshi; Harkema, Jack R.; Holian, Andrij; Pestka, James J.

    2015-01-01

    Genetic predisposition and environmental factors influence the development of human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased incidence of autoimmunity, including systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly understood. The purpose of this study was to test the hypothesis that early repeated short-term cSiO2 exposure will modulate both latency and severity of autoimmunity in the lupus-prone female NZBWF1 mouse. Weekly intranasal exposure to cSiO2 (0.25 and 1.0 mg) for 4 wk beginning at 9 wk of age both reduced latency and increased intensity of glomerulonephritis. cSiO2 elicited robust inflammatory responses in the lungs as evidenced by extensive perivascular and peribronchial lymphoplasmacytic infiltration consisting of IgG-producing plasma cells, and CD45R+ and CD3+ lymphocytes that were highly suggestive of ectopic lymphoid tissue (ELT). In addition, there were elevated concentrations of immunoglobulins and the cytokines MCP-1, TNF-α and IL-6 in bronchoalveolar lavage fluid. cSiO2-associated kidney and lung effects paralleled dose-dependent elevations of autoantibodies and proinflammatory cytokines in plasma. Taken together, cSiO2-induced pulmonary inflammation and ectopic lymphoid neogenesis in the NZBWF1 mouse corresponded closely to systemic inflammatory and autoimmune responses as well as the early initiation of pathological outcomes in the kidney. These findings suggest that following airway exposure to crystalline silica, in mice genetically prone to SLE, the lung serves as a platform for triggering systemic autoimmunity and glomerulonephritis. PMID:25978333

  10. Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging.

    PubMed

    Bernstein, Lori R; Mackenzie, Amelia C L; Kraemer, Duane C; Morley, John E; Farr, Susan; Chaffin, Charles L; Merchenthaler, István

    2014-06-01

    Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.

  11. Long-term cilostazol administration ameliorates memory decline in senescence-accelerated mouse prone 8 (SAMP8) through a dual effect on cAMP and blood-brain barrier.

    PubMed

    Yanai, Shuichi; Toyohara, Jun; Ishiwata, Kiichi; Ito, Hideki; Endo, Shogo

    2017-04-01

    Phosphodiesterases (PDEs), which hydrolyze and inactivate 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), play an important role in synaptic plasticity that underlies memory. Recently, several PDE inhibitors were assessed for their possible therapeutic efficacy in treating cognitive disorders. Here, we examined how cilostazol, a selective PDE3 inhibitor, affects brain functions in senescence-accelerated mouse prone 8 (SAMP8), an animal model of age-related cognitive impairment. Long-term administration of cilostazol restored the impaired context-dependent conditioned fear memory of SAMP8 to match that in normal aging control substrain SAMR1. Cilostazol also increased the number of cells containing phosphorylated cAMP-responsive element binding protein (CREB), a downstream component of the cAMP pathway. Finally, cilostazol improves blood-brain barrier (BBB) integrity, demonstrated by reduced extravasation of 2-deoxy-2-(18)F-fluoro-d-glucose and Evans Blue dye in the brains of SAMP8. This improvement in BBB integrity was associated with an increased amount of zona occludens protein 1 (ZO-1) and occludin proteins, components of tight junctions integral to the BBB. The results suggest that long-term administration of cilostazol exerts its beneficial effects on age-related cognitive impairment through a dual mechanism: by enhancing the cAMP system in the brain and by maintaining or improving BBB integrity.

  12. Moxidectin toxicity in senescence-accelerated prone and resistant mice.

    PubMed

    Lee, Vanessa K; Tiwary, Asheesh K; Sharma-Reddy, Prachi; Lieber, Karen A; Taylor, Douglas K; Mook, Deborah M

    2009-06-01

    Moxidectin has been used safely as an antiparasitic in many animal species, including for the eradication of the mouse fur mite, Mycoptes musculinus. Although no side effects of moxidectin have previously been reported to occur in mice, 2 strains of the senescence-accelerated mouse (SAMP8 and SAMR1) sustained considerable mortality after routine prophylactic treatment. To investigate the mechanism underlying this effect, moxidectin toxicosis in these mice was evaluated in a controlled study. Moxidectin was applied topically (0.015 mg), and drug concentrations in both brain and serum were analyzed by using HPLC coupled with mass spectrometry. The moxidectin concentration in brain of SAMP8 mice was 18 times that in controls, and that in brain of SAMR1 mice was 14 times higher than in controls, whereas serum moxidectin concentrations did not differ significantly among the 3 strains. Because deficiency of the blood-brain barrier protein P-glycoprotein leads to sensitivity to this class of drugs in other SAM mice, Pgp immunohistochemistry of brain sections from a subset of mice was performed to determine whether this commercially available analysis could predict sensitivity to this class of drug. The staining analysis showed no difference among the strains of mice, indicating that this test does not correlate with sensitivity. In addition, no gross or histologic evidence of organ toxicity was found in brain, liver, lung, or kidney. This report shows that topically applied moxidectin at a standard dose accumulates in the CNS causing toxicosis in both SAMP8 and SAMR1 mice.

  13. Chronic stress impairs learning and hippocampal cell proliferation in senescence-accelerated prone mice.

    PubMed

    Yan, Weihong; Zhang, Ting; Jia, Weiping; Sun, Xiaojiang; Liu, Xueyuan

    2011-02-25

    Chronic stress can induce cognitive impairment. It is unclear whether a higher susceptibility to chronic stress is associated with the progression of pathological brain aging. Senescence-accelerated prone mouse 8 (SAMP8) is a naturally occurring animal model of accelerated brain aging. Senescence-accelerated resistant mouse 1 (SAMR1) is usually used as the normal control. In this study, we examined the effects of chronic restraint stress (CRS) on learning in the Y-maze, hippocampal cell proliferation, and the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of 4-month-old SAMP8 and SAMR1. The results showed that exposure to CRS impaired learning and hippocampal cell proliferation in SAMP8 and SAMR1 but to a much greater extent in SAMP8. Furthermore, CRS significantly decreased the expression of BDNF protein and mRNA in the hippocampus of SAMP8 and SAMR1. These data indicated that SAMP8 is more sensitive to the deleterious effects of CRS on learning than SAMR1. A greater decrease in hippocampal cell proliferation caused by chronic stress may be part of the underlying mechanism for the more severe learning deficit observed in SAMP8. In addition, our findings suggested a role of BDNF in the stress-induced impairment of learning and hippocampal cell proliferation in both strains.

  14. Accelerated Whole Breast Irradiation With Intensity-Modulated Radiotherapy to the Prone Breast

    SciTech Connect

    Croog, Victoria J.; Wu, Abraham J.; McCormick, Beryl; Beal, Kathryn P.

    2009-01-01

    Purpose: Whole breast irradiation (WBI) is the standard of care for patients with early-stage breast cancer who opt for breast conservation. After a randomized trial demonstrated equivalent cosmesis and disease control with accelerated WBI (AWBI), our institution began to offer AWBI to appropriate patients. The aim of this study was to examine our unique experience with AWBI using prone positioning and simplified intensity-modulated radiotherapy (IMRT) planning with a sequential boost to the tumor bed. Methods and Materials: We identified 356 patients who had been treated with prone WBI using IMRT in our department between January 2004 and December 2006. Of these, 128 (36%) patients had received AWBI (representing 131 treated breasts), consisting of 16 daily fractions of 265 cGy to a total dose of 4,240 cGy followed by a conventionally fractionated boost. Results: Patients who opted for AWBI were similar demographically to the patients undergoing conventional WBI. In the AWBI cohort, 83% of the patients had Stage T1 disease and 22% had nodal involvement (N1). The tumors were estrogen receptor-positive, progesterone receptor-positive and Her-2/Neu-amplified in 82%, 69%, and 11%, respectively. The median duration of AWBI plus a boost was 29 days, and no patient required a toxicity-related treatment break. No Grade 3 or greater acute toxicity developed. At a median follow-up of 18 months, one ipsilateral breast recurrence developed that was salvaged with mastectomy and immediate reconstruction. Conclusion: AWBI to the prone breast using simplified IMRT with a sequential boost offers women requiring breast-only adjuvant radiotherapy an abbreviated treatment with early tumor control and cosmesis comparable to that with standard fractionation.

  15. Melatonin improves inflammation processes in liver of senescence-accelerated prone male mice (SAMP8).

    PubMed

    Cuesta, Sara; Kireev, Roman; Forman, Katherine; García, Cruz; Escames, Germaine; Ariznavarreta, Carmen; Vara, Elena; Tresguerres, Jesús A F

    2010-12-01

    Aging is associated with an increase in oxidative stress and inflammation. The aim of this study was to investigate the effect of aging on various physiological parameters related to inflammation in livers obtained from two types of male mice models: Senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant (SAMR1) mice, and to study the influence of the administration of melatonin (1mg/kg/day) for one month on old SAMP8 mice on these parameters. The parameters studied have been the mRNA expression of TNF-α, iNOS, IL-1β, HO-1, HO-2, MCP1, NFkB1, NFkB2, NFkB protein or NKAP and IL-10. All have been measured by real-time reverse transcription polymerase chain reaction RT-PCR. Furthermore we analyzed the protein expression of TNF-α, iNOS, IL-1β, HO-1, HO-2, and IL-10 by Western-blot. Aging increased oxidative stress and inflammation especially in the liver of SAMP8 mice. Treatment with melatonin decreased the mRNA expression of TNF-α, IL-1β, HO (HO-1 and HO-2), iNOS, MCP1, NFκB1, NFκB2 and NKAP in old male mice. The protein expression of TNF-α, IL-1β was also decreased and IL-10 increased with melatonin treatment and no significant differences were observed in the rest of parameters analyzed. The present study showed that aging was related to inflammation in livers obtained from old male senescence prone mice (SAMP8) and old male senescence resistant mice (SAMR1) being the alterations more evident in the former. Exogenous administration of melatonin was able to reduce inflammation.

  16. PRONE ACCELERATED PARTIAL BREAST IRRADIATION AFTER BREAST-CONSERVING SURGERY: FIVE YEAR RESULTS OF 100 PATIENTS

    PubMed Central

    Formenti, Silvia C.; Hsu, Howard; Fenton-Kerimian, Maria; Roses, Daniel; Guth, Amber; Jozsef, Gabor; Goldberg, Judith D.; DeWyngaert, J. Keith

    2013-01-01

    Purpose To report the 5-year results of a prospective trial of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation in the prone position (P-APBI). Methods Post-menopausal patients with Stage I breast cancer with non palpable <2 cm tumors, negative margins, and negative nodes, positive hormonal receptors, and no extensive intraductal component (EIC) were eligible. The trial was offered only once eligible patients had refused to undergo standard whole-breast radiotherapy. Patients were simulated and treated on a dedicated table for prone set-up. The 3D-CRT delivered was 30 Gy in five 6 Gy/daily fractions over 10 days with port film verification at each treatment. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Disease-free, overall, and cancer-specific survival (DFS, OS, CSS) were recorded. Results One hundred patients accrued to this IRB- approved prospective trial, one with bilateral breast cancer. One patient withdrew consent after simulation and another elected to interrupt radiotherapy after receiving two treatments. Ninety-eight patients are evaluable for toxicity and, in one case, both breasts were treated with PBI. Median patient age was 68 years (range 53–88 years); in 55% the tumor size was <1 cm. All patients had hormonal receptor positive cancers: 87% underwent adjuvant anti-hormonal therapy. At a median follow-up of 64 months (range, 2–125 months), there was one local recurrence (1% IBF) and one contralateral breast cancer (1% CBF). There were no deaths due to breast cancer by 5 years. Grade 3 late toxicities occurred in 2 patients (1 breast edema, 1 transient breast pain). Cosmesis was rated good/excellent in 89% of patients with at least 36 months follow-up. Conclusions Five-year efficacy and toxicity of 3D-CRT to deliver prone-PBI are comparable to other experiences with similar

  17. Acupuncture promotes mTOR-independent autophagic clearance of aggregation-prone proteins in mouse brain.

    PubMed

    Tian, Tian; Sun, Yanhong; Wu, Huangan; Pei, Jian; Zhang, Jing; Zhang, Yi; Wang, Lu; Li, Bin; Wang, Lihua; Shi, Jiye; Hu, Jun; Fan, Chunhai

    2016-01-21

    Acupuncture has historically been practiced to treat medical disorders by mechanically stimulating specific acupoints with fine needles. Despite its well-documented efficacy, its biological basis remains largely elusive. In this study, we found that mechanical stimulation at the acupoint of Yanglingquan (GB34) promoted the autophagic clearance of α-synuclein (α-syn), a well known aggregation-prone protein closely related to Parkinson's disease (PD), in the substantia nigra par compacta (SNpc) of the brain in a PD mouse model. We found the protein clearance arose from the activation of the autophagy-lysosome pathway (ALP) in a mammalian target of rapamycin (mTOR)-independent approach. Further, we observed the recovery in the activity of dopaminergic neurons in SNpc, and improvement in the motor function at the behavior level of PD mice. Whereas acupuncture and rapamycin, a chemical mTOR inhibitor, show comparable α-syn clearance and therapeutic effects in the PD mouse model, the latter adopts a distinctly different, mTOR-dependent, autophagy induction process. Due to this fundamental difference, acupuncture may circumvent adverse effects of the rapamycin treatment. The newly discovered connection between acupuncture and autophagy not only provides a new route to understanding the molecular mechanism of acupuncture but also sheds new light on cost-effective and safe therapy of neurodegenerative diseases.

  18. Interleukin-1β Accelerates the Onset of Stroke in Stroke-Prone Spontaneously Hypertensive Rats

    PubMed Central

    Chiba, Tsuyoshi; Itoh, Tatsuki; Tabuchi, Masaki; Nakazawa, Toru; Satou, Takao

    2012-01-01

    High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP). At 4 weeks of age (before stroke onset), the plasma level of IL-1β was significantly higher in SHRSP (153.0 ± 49.7 pg/ml) than in Wistar Kyoto rats (WKY) (7.7 ± 3.4 pg/ml, P < 0.001 versus SHRSP) or spontaneously hypertensive rats (SHR) (28.0 ± 9.1 pg/ml, P < 0.001 versus SHRSP) (n = 6 per strain). Stimulated IL-1β signal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1), which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β (2 μg/day) using an osmotic pump slightly increased the incidence of stroke in SHR (P = 0.046) and significantly accelerated the onset of stroke in SHRSP (P = 0.006) compared to each control (n = 10 per group). These results suggest that a stimulated IL-1β signal might be a cause of stroke onset when concomitant with severe hypertension. PMID:23326018

  19. Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Compliance to the Dosimetry Requirements of RTOG-0413

    SciTech Connect

    Wen Bixiu; Hsu, Howard; Formenti-Ujlaki, George F.; Lymberis, Stella; Magnolfi, Chiara; Zhao Xuan; Chang Jenghwa; DeWyngaert, J. Keith; Jozsef, Gabor; Formenti, Silvia C.

    2012-11-15

    Purpose: The dosimetric results from our institution's trials of prone accelerated partial breast irradiation are compared with the dosimetric requirements of RTOG-0413. Methods and Materials: Trial 1 and Trial 2 are 2 consecutive trials of prone-accelerated partial breast irradiation. Eligible for both trials were stage I breast cancer patients with negative margins after breast-conserving surgery. The planning target tumor volume (PTV) was created by extending the surgical cavity 2.0 cm for Trial 1 and 1.5 cm for Trial 2, respectively. Contralateral breast, heart, lungs, and thyroid were contoured. Thirty Gray was delivered in five daily fractions of 6 Gy by a three-dimensional conformal radiation therapy technique in Trial 1 and were by image-guided radiation therapy/intensity-modulated radiation therapy in Trial 2. Dosimetric results from the trials are reported and compared with RTOG 0413 requirements. Results: One hundred forty-six consecutive plans were analyzed: 67 left and 79 right breast cancers. The plans from the trials complied with the required >90% of prescribed dose covering 90% of PTV{sub E}VAL (=generated from the PTV by cropping 0.5 cm from the skin edge and excluding the chest wall): V90% was 98.1 {+-} 3.0% (with V100% and V95%, 89.4 {+-} 12.8%, 96.4 {+-} 5.1%, respectively). No significant difference between laterality was found (Student's t test). The dose constraints criteria of the RTOG-0413 protocol for ipsilateral and contralateral lung (V30 <15% and Dmax <3%), heart (V5 <40%), and thyroid (Dmax <3%) were satisfied because the plans showed an average V5% of 0.6% (range, 0-13.4) for heart, an average V30% of 0.6% (range, 0-9.1%) for ipsilateral lung, and <2% maximum dose to the thyroid. However, our partial breast irradiation plans demonstrated a higher dose to contralateral breast than that defined by RTOG constraints, with a median value of maximum doses of 4.1% (1.2 Gy), possibly as a result of contouring differences. Conclusions: Our

  20. Prospective Study of Cone-Beam Computed Tomography Image-Guided Radiotherapy for Prone Accelerated Partial Breast Irradiation

    SciTech Connect

    Jozsef, Gabor; DeWyngaert, J. Keith; Becker, Stewart J.; Lymberis, Stella; Formenti, Silvia C.

    2011-10-01

    Purpose: To report setup variations during prone accelerated partial breast irradiation (APBI). Methods: New York University (NYU) 07-582 is an institutional review board-approved protocol of cone-beam computed tomography (CBCT) to deliver image-guided ABPI in the prone position. Eligible are postmenopausal women with pT1 breast cancer excised with negative margins and no nodal involvement. A total dose of 30 Gy in five daily fractions of 6 Gy are delivered to the planning target volume (the tumor cavity with 1.5-cm margin) by image-guided radiotherapy. Patients are set up prone, on a dedicated mattress, used for both simulation and treatment. After positioning with skin marks and lasers, CBCTs are performed and the images are registered to the planning CT. The resulting shifts (setup corrections) are recorded in the three principal directions and applied. Portal images are taken for verification. If they differ from the planning digital reconstructed radiographs, the patient is reset, and a new CBCT is taken. Results: 70 consecutive patients have undergone a total of 343 CBCTs: 7 patients had four of five planned CBCTs performed. Seven CBCTs (2%) required to be repeated because of misalignment in the comparison between portal and digital reconstructed radiograph image after the first CBCT. The mean shifts and standard deviations in the anterior-posterior (AP), superior-inferior (SI), and medial-lateral (ML) directions were -0.19 (0.54), -0.02 (0.33), and -0.02 (0.43) cm, respectively. The average root mean squares of the daily shifts were 0.50 (0.28), 0.29 (0.17), and 0.38 (0.20). A conservative margin formula resulted in a recommended margin of 1.26, 0.73, 0.96 cm in the AP, SI, and ML directions. Conclusion: CBCTs confirmed that the NYU prone APBI setup and treatment technique are reproducible, with interfraction variation comparable to those reported for supine setup. The currently applied margin (1.5 cm) adequately compensates for the setup variation detected.

  1. Mutagenic safety and fatty liver improvement of nanonized black soybeans in senescence-accelerated prone-8 mice.

    PubMed

    Liao, J-W; Hong, L-Z; Wang, M-F; Tsai, S-C; Lin, Y-J; Chan, Y-C

    2010-06-01

    Nanotechnology, as a new enabling technology, has the potential to revolutionize food systems. However, much attention has been focused on nanoparticle foods due to their potential physiological properties. This study was aimed to evaluate the mutagenic safety and fatty liver improvement of black soybean in senescence-accelerated mice (SAMP8). The mutagenic activity of black soybeans was investigated using the Ames test (Salmonella Typhimurium TA98, 100, 102, and 1535). Furthermore, senescence-accelerated prone-8 mice (SAMP8) have been reported to display spontaneous fatty liver. Male SAMP8 mice were divided into control and supplemented with 10% micronized or nanonized black soybeans diet and fed for 12 wk. The results revealed that the Ames test of micronized and nanonized black soybeans exhibited no mutagenicity. Administration of black soybeans to mice showed no effects on food intake and body and organ weights. The nanonized black soybean group had a lower degree of spontaneous fatty liver, alanine aminotransferase, and thiobarbituric acid-reactive substance concentrations, and had enhanced superoxide dismutase, catalase, and glutathione peroxidase activities of livers when compared with the SAMP8 control and micronized black soybean groups. The mice fed with black soybeans had significantly lower triglyceride concentrations than the SAMP8 control group. The results of this study suggest that nanonized black soybeans have no side effects and, moreover, may minimize liver lesions in SAMP8 mice.

  2. [Morphological changes of neurons and neuroglial cells in the brain of senescence-accelerated prone 1 (SAMP1) mice].

    PubMed

    Khudoerkov, R M; Sal'kov, V N; Sal'nikova, O V; Sobolev, V B

    2014-01-01

    Computerized morphometry was used to examine the sizes of neuronal bodies and the compactness of arrangement of neurons and neuroglial cells in layers III and V of the sensorimotor cortex in senescence-accelerated prone 1 (SAMP1) mice (an experimental group) and senescence-accelerated-resistant strain 1 (SAMR1) ones (a control group). In the SAMP1 mice as compared to the SAMR1 ones, the neuronal body sizes were significantly unchanged; the compactness of their arrangement decreased by 17 and 20% in layers III and V, respectively; that of neuroglial cells significantly increased by 14% in layer III only. In the SAMP1 mice versus the SAMR1 ones, the glial index rose by 36% in layer III and by 24% in layer V. During simulation of physiological aging, the sizes of neuronal bodies were shown to be virtually unchanged in the cerebral cortex; the compactness of their arrangement (cell counts) moderately reduced and that of neuroglial cells increased, which caused a rise in the glioneuronal index that was indicative of the enhanced supporting function of neuroglial cells during the physiological aging of brain structures.

  3. Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

    PubMed

    Tomobe, Koji; Fujii, Hajime; Sun, Buxiang; Nishioka, Hiroshi; Aruoma, Okezie I

    2007-08-01

    Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the

  4. Western-style diet modulates contractile responses to phenylephrine differently in mesenteric arteries from senescence-accelerated prone (SAMP8) and resistant (SAMR1) mice.

    PubMed

    Jiménez-Altayó, Francesc; Onetti, Yara; Heras, Magda; Dantas, Ana P; Vila, Elisabet

    2013-08-01

    The influence of two known cardiovascular risk factors, aging and consumption of a high-fat diet, on vascular mesenteric artery reactivity was examined in a mouse model of accelerated senescence (SAM). Five-month-old SAM prone (SAMP8) and resistant (SAMR1) female mice were fed a Western-type high-fat diet (WD; 8 weeks). Mesenteric arteries were dissected, and vascular reactivity, protein and messenger RNA expression, superoxide anion (O 2 (·-) ) and hydrogen peroxide formation were evaluated by wire myography, immunofluorescence, RT-qPCR, ethidium fluorescence and ferric-xylenol orange, respectively. Contraction to KCl and relaxation to acetylcholine remained unchanged irrespective of senescence and diet. Although similar contractions to phenylephrine were observed in SAMR1 and SAMP8, accelerated senescence was associated with decreased eNOS and nNOS and increased O 2 (·-) synthesis. Senescence-related alterations were compensated, at least partly, by the contribution of NO derived from iNOS and the enhanced endogenous antioxidant capacity of superoxide dismutase 1 to maintain vasoconstriction. Administration of a WD induced qualitatively different alterations in phenylephrine contractions of mesenteric arteries from SAMR1 and SAMP8. SAMR1 showed increased contractions partly as a result of decreased NO availability generated by decreased eNOS and nNOS and enhanced O 2 (·-) formation. In contrast, WD feeding in SAMP8 resulted in reduced contractions due to, at least in part, the increased functional participation of iNOS-derived NO. In conclusion, senescence-dependent intrinsic alterations during early stages of vascular senescence may promote vascular adaptation and predispose to further changes in response to high-fat intake, which may lead to the progression of aging-related cardiovascular disease, whereas young subjects lack the capacity for this adaptation.

  5. Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Five-year Results of 100 Patients

    SciTech Connect

    Formenti, Silvia C.; Hsu, Howard; Fenton-Kerimian, Maria; Roses, Daniel; Guth, Amber; Jozsef, Gabor; Goldberg, Judith D.; DeWyngaert, J. Keith

    2012-11-01

    Purpose: To report the 5-year results of a prospective trial of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation in the prone position. Methods and Materials: Postmenopausal patients with Stage I breast cancer with nonpalpable tumors <2 cm, negative margins and negative nodes, positive hormone receptors, and no extensive intraductal component were eligible. The trial was offered only after eligible patients had refused to undergo standard whole-breast radiotherapy. Patients were simulated and treated on a dedicated table for prone setup. 3D-CRT was delivered at a dose of 30 Gy in five 6-Gy/day fractions over 10 days with port film verification at each treatment. Rates of ipsilateral breast failure, ipsilateral nodal failure, contralateral breast failure, and distant failure were estimated using the cumulative incidence method. Rates of disease-free, overall, and cancer-specific survival were recorded. Results: One hundred patients were enrolled in this institutional review board-approved prospective trial, one with bilateral breast cancer. One patient withdrew consent after simulation, and another patient elected to interrupt radiotherapy after receiving two treatments. Ninety-eight patients were evaluable for toxicity, and, in 1 case, both breasts were treated with partial breast irradiation. Median patient age was 68 years (range, 53-88 years); in 55% of patients the tumor size was <1 cm. All patients had hormone receptor-positive cancers: 87% of patients underwent adjuvant antihormone therapy. At a median follow-up of 64 months (range, 2-125 months), there was one local recurrence (1% ipsilateral breast failure) and one contralateral breast cancer (1% contralateral breast failure). There were no deaths due to breast cancer by 5 years. Grade 3 late toxicities occurred in 2 patients (one breast edema, one transient breast pain). Cosmesis was rated good/excellent in 89% of patients with at least 36

  6. Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8).

    PubMed

    Cuesta, Sara; Kireev, Roman; García, Cruz; Rancan, Lisa; Vara, Elena; Tresguerres, Jesús A F

    2013-06-01

    The aim of the present study was to investigate the effect of aging on several parameters related to glucose homeostasis and insulin resistance in pancreas and how melatonin administration could affect these parameters. Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant mice (SAMR1). Insulin levels in plasma were increased with aging in both SAMP8 and SAMR1 mice, whereas insulin content in pancreas was decreased with aging in SAMP8 and increased in SAMR1 mice. Expressions of glucagon and GLUT2 messenger RNAs (mRNAs) were increased with aging in SAMP8 mice, and no differences were observed in somatostatin and insulin mRNA expressions. Furthermore, aging decreased also the expressions of Pdx-1, FoxO 1, FoxO 3A and Sirt1 in pancreatic SAMP8 samples. Pdx-1 was decreased in SAMR1 mice, but no differences were observed in the rest of parameters on these mice strains. Treatment with melatonin was able to decrease plasma insulin levels and to increase its pancreatic content in SAMP8 mice. In SAMR1, insulin pancreatic content and plasma levels were decreased. HOMA-IR was decreased with melatonin treatment in both strains of animals. On the other hand, in SAMP8 mice, treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin mRNA. Furthermore, it was also able to increase the expression of Sirt1, Pdx-1 and FoxO 3A. According to these results, aging is associated with significant alterations in the relative expression of pancreatic genes associated to glucose metabolism. This has been especially observed in SAMP8 mice. Melatonin administration was able to improve pancreatic function in old SAMP8 mice and to reduce HOMA-IR improving their insulin physiology and glucose metabolism.

  7. Aberrant expression of PDGF ligands and receptors in the tumor prone ovary of follitropin receptor knockout (FORKO) mouse.

    PubMed

    Chen, Xinlei; Aravindakshan, Jayaprakash; Yang, Yinzhi; Tiwari-Pandey, Rashmi; Sairam, M Ram

    2006-05-01

    Although PDGF family members play a vital role in cell proliferation, motility and chemotaxis via activation of structurally similar alpha- and beta-receptors, little is known of their function in ovarian regulation and induction of tumorigenesis. Microarray analyses of ovaries from young follitropin receptor knockout (FORKO) mice that are prone to late ovarian tumors upon aging have revealed significant imbalances in PDGF ligands and receptors. We hypothesized that FSH/FSH-R signaling may exert effects partly by regulation of PDGF the family. To further understand their implications for ovarian tumorigenesis, we studied FORKO ovaries and hormonal regulation of the PDGF family members in normal mice, by using RT-PCR, Q-PCR, immunohistochemistry and western blotting. While PDGF-C and PDGFR-alpha increased, PDGFR-beta mRNA and protein decreased significantly in absence of FSH-R signaling. In the normal ovary, PDGFR-alpha was not affected by gonadotropin (eCG) stimulation but PDGF-C and PDGFR-beta decreased. Administration of estradiol decreased PDGF and their receptors. To further probe the differential regulation of PDGF family members by eCG and estradiol, we co-administered eCG with estrogen antagonist, ICI 182780. Increase in PDGFR-alpha in the absence of estradiol suggests direct effects of FSH signaling. During the estrous cycle in mice PDGF-C, PDGF-D and PDGFR-alpha mRNA levels were higher at the proestrous. By IHC, we report for the first time the localization of PDGF-C, PDGFR-alpha and PDGFR-beta protein in mouse ovarian compartments including the surface epithelium that is also altered in mutants. Immunostaining of PDGFRs increased as the follicle developed to preantral stage and declined thereafter. Thus, FSH modulates PDGF family members, partly via E2, suggesting that loss of FSH-R signaling causes an imbalance of PDGF family members predisposing the abnormal ovarian follicular environment for inducing tumorigenesis in aging FORKO mice.

  8. MO-DE-210-06: Development of a Supercompounded 3D Volumetric Ultrasound Image Guidance System for Prone Accelerated Partial Breast Irradiation (APBI)

    SciTech Connect

    Chiu, T; Hrycushko, B; Zhao, B; Jiang, S; Gu, X

    2015-06-15

    Purpose: For early-stage breast cancer, accelerated partial breast irradiation (APBI) is a cost-effective breast-conserving treatment. Irradiation in a prone position can mitigate respiratory induced breast movement and achieve maximal sparing of heart and lung tissues. However, accurate dose delivery is challenging due to breast deformation and lumpectomy cavity shrinkage. We propose a 3D volumetric ultrasound (US) image guidance system for accurate prone APBI Methods: The designed system, set beneath the prone breast board, consists of a water container, an US scanner, and a two-layer breast immobilization cup. The outer layer of the breast cup forms the inner wall of water container while the inner layer is attached to patient breast directly to immobilization. The US transducer scans is attached to the outer-layer of breast cup at the dent of water container. Rotational US scans in a transverse plane are achieved by simultaneously rotating water container and transducer, and multiple transverse scanning forms a 3D scan. A supercompounding-technique-based volumetric US reconstruction algorithm is developed for 3D image reconstruction. The performance of the designed system is evaluated with two custom-made gelatin phantoms containing several cylindrical inserts filled in with water (11% reflection coefficient between materials). One phantom is designed for positioning evaluation while the other is for scaling assessment. Results: In the positioning evaluation phantom, the central distances between the inserts are 15, 20, 30 and 40 mm. The distances on reconstructed images differ by −0.19, −0.65, −0.11 and −1.67 mm, respectively. In the scaling evaluation phantom, inserts are 12.7, 19.05, 25.40 and 31.75 mm in diameter. Measured inserts’ sizes on images differed by 0.23, 0.19, −0.1 and 0.22 mm, respectively. Conclusion: The phantom evaluation results show that the developed 3D volumetric US system can accurately localize target position and determine

  9. The MeCP2-null mouse hippocampus displays altered basal inhibitory rhythms and is prone to hyperexcitability.

    PubMed

    Zhang, Liang; He, Jiwei; Jugloff, Denis G M; Eubanks, James H

    2008-01-01

    Rett syndrome is an autism-spectrum disorder caused by loss of function mutations within the gene encoding methyl CpG-binding protein 2 (MeCP2). While subtle decreases in synaptic plasticity have been detected within cortical and hippocampal neurons of Mecp2-null mice, only minimal information exists regarding how the loss of MeCP2 affects network activity in the brain. To address this issue, we compared the intrinsic network activities of Mecp2-null hippocampal slices derived from symptomatic mice to wild-type slices. Extracellular and whole-cell patch recordings revealed that although spontaneous, IPSP-based rhythmic activity is present in Mecp2-null slices; its frequency is significantly reduced from wild-type. This reduction was not associated with alterations in the gross electrophysiological properties of hippocampal neurons, but was associated with a decreased level of spontaneous glutamate receptor-mediated synaptic currents in hippocampal CA3 neurons. Paradoxically, however, repetitive sharp wave-like discharges were readily induced in the Mecp2-null hippocampal slices by a brief train of high-frequency stimulation commonly used to establish long-term potentiation at wild-type slices. Taken together, our data indicate that the Mecp2-null hippocampal CA3 circuit has diminished basal inhibitory rhythmic activity, which in turn renders the circuitry prone to hyperexcitability.

  10. A Dosimetric Comparison of Accelerated Partial Breast Irradiation Techniques: Multicatheter Interstitial Brachytherapy, Three-Dimensional Conformal Radiotherapy, and Supine Versus Prone Helical Tomotherapy

    SciTech Connect

    Patel, Rakesh R. . E-mail: patel@humonc.wisc.edu; Becker, Stewart J.; Das, Rupak K.; Mackie, Thomas R.

    2007-07-01

    Purpose: To compare dosimetrically four different techniques of accelerated partial breast irradiation (APBI) in the same patient. Methods and Materials: Thirteen post-lumpectomy interstitial brachytherapy (IB) patients underwent imaging with preimplant computed tomography (CT) in the prone and supine position. These CT scans were then used to generate three-dimensional conformal radiotherapy (3D-CRT) and prone and supine helical tomotherapy (PT and ST, respectively) APBI plans and compared with the treated IB plans. Dose-volume histogram analysis and the mean dose (NTD{sub mean}) values were compared. Results: Planning target volume coverage was excellent for all methods. Statistical significance was considered to be a p value <0.05. The mean V100 was significantly lower for IB (12% vs. 15% for PT, 18% for ST, and 26% for 3D-CRT). A greater significant differential was seen when comparing V50 with mean values of 24%, 43%, 47%, and 52% for IB, PT, ST, and 3D-CRT, respectively. The IB and PT were similar and delivered an average lung NTD{sub mean} dose of 1.3 Gy{sub 3} and 1.2 Gy{sub 3}, respectively. Both of these methods were statistically significantly lower than the supine external beam techniques. Overall, all four methods yielded similar low doses to the heart. Conclusions: The use of IB and PT resulted in greater normal tissue sparing (especially ipsilateral breast and lung) than the use of supine external beam techniques of 3D-CRT or ST. However, the choice of APBI technique must be tailored to the patient's anatomy, lumpectomy cavity location, and overall treatment goals.

  11. SU-E-T-217: Comprehensive Dosimetric Evaluation On 3D-CRT, IMRT and Non-Coplanar Arc Treatment for Prone Accelerated Partial Breast Irradiation (APBI)

    SciTech Connect

    Chiu, T; Yan, Y; Ramirez, E; Lee, P; Jiang, S; Gu, X

    2015-06-15

    Purpose: Accelerated partial breast irradiation (APBI) is an effective treatment for early stage breast-cancer. Irradiation in a prone position can mitigate breast motion and spare heart and lung. In this study, a comprehensive study is performed to evaluate various treatment techniques for prone APBI treatment including: 3D-CRT, IMRT, co-planar and non-coplanar partial arcs treatment. Methods: In this treatment planning study, a left breast patient treated in prone position in our clinic was imported into Varian Eclipse TPS. Six beams tangential to chest wall were used in both 3D-CRT and IMRT plans. These six beams were coplanar in a transactional plane achieved by both gantry and couch rotation. A 60-beam IMRT plan was also created to explore the maximum benefit of co-planar IMRT. Within deliverable couch rotation range (±30°), partial arc treatment plans with one and up to ten couch positions were generated for comparison. For each plan, 30Gy in 6 fractions was prescribed to 95% PTV volume. Critical dosimetric parameters, such as conformity index, mean, maximum, and volume dose of organ at risk, are evaluated. Results: The conformity indexes (CI) are 3.53, 3.17, 2.21 and 1.08 respectively to 3D-CRT, 6-beam IMRT, 60-beam IMRT, and two-partial-arcs coplanar plans. However, arc plans increase heart dose. CI for non-coplanar arc plans decreases from 1.19 to 1.10 when increases couch positions. Maximum dose in ipsilateral lung (1.98 to 1.13 Gy), and heart (0.62 to 0.43 Gy) are steadily decreased with the increased number of non-coplanar arcs. Conclusions: The dosimetric evaluation results show that partial arc plans have improved CIs compared to conventional 3D-CRT and IMRT plans. Increasing number of partial arcs decreases lung and heart dose. The dosimetric benefit obtained from non-coplanar arcs should be considered with treatment delivery time.

  12. The role of NK cell activity in the pathogenesis of poly I:C accelerated and spontaneous diabetes in the diabetes prone BB rat.

    PubMed

    Sobel, D O; Azumi, N; Creswell, K; Holterman, D; Blair, O C; Bellanti, J A; Abbassi, V; Hiserodt, J C

    1995-12-01

    The development of insulin dependent diabetes mellitus (IDDM) and diabetes in the diabetes prone (DP) BB rat animal model of IDDM is thought to be due to an autoimmune process. Natural killer (NK) cells have been implicated but not proven to play a pathogenetic role in BB rats due to the increased NK cell number and activity found in these animals. We have recently reported that poly I:C, an inducer of cytokines and a potent enhancer of NK cell function, accelerates the development of diabetes in DP BB rats and induces diabetes in diabetes resistant (DR) BB rats. Since we have further demonstrated that poly I:C administration to BB rats increases NK cell number and levels of inducers of NK cell activity, interferon-alpha and IL-6 which is described therein, we tested the hypothesis that NK cell activity plays an important role in poly I:C accelerated disease. The role of NK cells in poly I:C accelerated diabetes and spontaneous diabetes was examined by determining whether selective depletion of NK cells using a rat NK cell specific antibody (anti-NKR-P1 antibody) alters the development of diabetes. The treatment of BB rats with anti-NKR-P1 antibody resulted in a significantly lower mean NK cell activity of splenic mononuclear cells than that found in control animals. However, the development of diabetes and degree of insulitis was not significantly different between treatment groups. BB rats administered anti-NKR-P1 antibody with poly I:C had a lower mean splenocyte NK cell activity and lower mean NK cell number within the peripheral blood and inflamed islets than rats administered poly I:C alone. However, anti-NKR-P1 antibody administration did not alter the accelerated development of diabetes or the degree of insulitis in poly I:C treated animals. These data document that NK cells do not play a major role in the pathogenesis of poly I:C accelerated diabetes or spontaneous diabetes in the DP BB rat.

  13. Age-related alterations in the expression of glial cell line-derived neurotrophic factor in the senescence-accelerated mouse brain.

    PubMed

    Miyazaki, Hiroyuki; Okuma, Yasunobu; Nomura, Jun; Nagashima, Kazuo; Nomura, Yasuyuki

    2003-05-01

    Senescence-accelerated mouse prone 8 (SAMP8) and prone 10 (SAMP10) are useful murine model of accelerated aging. SAMP8 shows marked impairment of learning and memory, whereas SAMP10 shows brain atrophy and aging-associated depressive behavior. This study examined the expression of glial cell line-derived neurotrophic factor (GDNF) in SAMP8 and SAMP10 brains, relative to that in SAM resistant 1 (SAMR1) controls, which age normally. Hippocampal GDNF mRNA expression decreased in an age-dependent manner (10- vs 2-month-old animals) in the SAMR1, but not in the SAMP8 or SAMP10 strains. Furthermore, GDNF mRNA expression in 2-month-old SAMP8 and SAMP10 strains was less than in SAMR1 specimens of the same age. The number of surviving neurons in the CA1 region decreased with age in SAMP8 and SAMP10, and also decreased relative to the number of neurons in 10-month-old SAMR1 controls. Immunohistochemistry revealed that cells that were positive for GDNF-like activity in 10-month-old SAMP8 and SAMP10 were diffusely distributed, in part, around the pyramidal cell layer in the hippocampus. These findings suggest that low GDNF expression in young SAMP8 and SAMP10 may be involved in hippocampal dysfunctions, such as age-related learning impairment and neuronal death.

  14. Accelerated high-frame-rate mouse heart cine-MRI using compressed sensing reconstruction.

    PubMed

    Motaal, Abdallah G; Coolen, Bram F; Abdurrachim, Desiree; Castro, Rui M; Prompers, Jeanine J; Florack, Luc M J; Nicolay, Klaas; Strijkers, Gustav J

    2013-04-01

    We introduce a new protocol to obtain very high-frame-rate cinematographic (Cine) MRI movies of the beating mouse heart within a reasonable measurement time. The method is based on a self-gated accelerated fast low-angle shot (FLASH) acquisition and compressed sensing reconstruction. Key to our approach is that we exploit the stochastic nature of the retrospective triggering acquisition scheme to produce an undersampled and random k-t space filling that allows for compressed sensing reconstruction and acceleration. As a standard, a self-gated FLASH sequence with a total acquisition time of 10 min was used to produce single-slice Cine movies of seven mouse hearts with 90 frames per cardiac cycle. Two times (2×) and three times (3×) k-t space undersampled Cine movies were produced from 2.5- and 1.5-min data acquisitions, respectively. The accelerated 90-frame Cine movies of mouse hearts were successfully reconstructed with a compressed sensing algorithm. The movies had high image quality and the undersampling artifacts were effectively removed. Left ventricular functional parameters, i.e. end-systolic and end-diastolic lumen surface areas and early-to-late filling rate ratio as a parameter to evaluate diastolic function, derived from the standard and accelerated Cine movies, were nearly identical.

  15. Ribose Accelerates Gut Motility and Suppresses Mouse Body Weight Gaining

    PubMed Central

    Liu, Yan; Li, Tong-Ruei R; Xu, Cong; Xu, Tian

    2016-01-01

    The increasing prevalence of obesity is closely related to excessive energy consumption. Clinical intervention of energy intake is an attractive strategy to fight obesity. However, the current FDA-approved weight-loss drugs all have significant side effects. Here we show that ribose upregulates gut motility and suppresses mice body weight gain. Ribokinase, which is encoded by Rbks gene, is the first enzyme for ribose metabolism in vivo. Rbks mutation resulted in ribose accumulation in the small intestine, which accelerated gut movement. Ribose oral treatment in wild type mice also enhanced bowel motility and rendered mice resistance to high fat diets. The suppressed weight gain was resulted from enhanced ingested food excretion. In addition, the effective dose of ribose didn't cause any known side effects (i.e. diarrhea and hypoglycemia). Overall, our results show that ribose can regulate gut motility and energy homeostasis in mice, and suggest that administration of ribose and its analogs could regulate gastrointestinal motility, providing a novel therapeutic approach for gastrointestinal dysfunction and weight control. PMID:27194947

  16. Defects in cytokine-mediated neuroprotective glial responses to excitotoxic hippocampal injury in senescence-accelerated mouse.

    PubMed

    Hasegawa-Ishii, Sanae; Takei, Shiro; Inaba, Muneo; Umegaki, Hiroyuki; Chiba, Yoichi; Furukawa, Ayako; Kawamura, Noriko; Hosokawa, Masanori; Shimada, Atsuyoshi

    2011-01-01

    Aging is a result of damage accumulation, and understanding of the mechanisms of aging requires exploration of the cellular and molecular systems functioning to control damage. Senescence-accelerated mouse prone 10 (SAMP10) has been established as an inbred strain exhibiting accelerated aging with an earlier onset of cognitive impairment due to neurodegeneration than the senescence-resistant control (SAMR1) strain. We hypothesized that tissue-protective responses of glial cells are impaired in SAMP10 mice. We injected kainic acid (KA) to induce hippocampal injury and studied how cytokines were upregulated on Day 3 using 3-month-old SAMP10 and SAMR1 mice. Following microarray-based screening for upregulated genes, we performed real-time RT-PCR and immunohistochemistry. Results indicated well-orchestrated cytokine-mediated glial interactions in the injured hippocampus of SAMR1 mice, in which microglia-derived interferon (IFN)-γ stimulated astrocytes via IFN-γ receptor and thereby induced expression of CXCL10 and macrophage inflammatory protein (MIP)-1α, and activated microglia produced granulocyte-macrophage colony-stimulating factor (GM-CSF) and osteopontin (OPN). OPN was the most strongly upregulated cytokine. CD44, an OPN receptor, was also strongly upregulated in the neuropil, especially on neurons and astrocytes. KA-induced hippocampal upregulation of these cytokines was strikingly reduced in SAMP10 mice compared to SAMR1 mice. On Day 30 after KA injection, SAMP10 but not SAMR1 mice exhibited hippocampal layer atrophy. Since the OPN-CD44 system is essential for neuroprotection and remodeling, these findings highlight the defects of SAMP10 mice in cytokine-mediated neuroprotective glia-neuron interactions, which may be associated with the mechanism underlying the vulnerability of SAMP10 mice to age-related neurodegeneration.

  17. Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea.

    PubMed

    Lee, Koon-Ja; Lee, Ji-Young; Lee, Sung Ho; Choi, Tae Hoon

    2013-04-01

    To understand the corneal regeneration induced by bevacizumab, we investigated the structure changes of stroma and basement membrane regeneration. A Stick soaked in 0.5 N NaOH onto the mouse cornea and 2.5 mg/ml of bevacizumab was delivered into an alkali-burned cornea (2 μl) by subconjunctival injections at 1 hour and 4 days after injury. At 7 days after injury, basement membrane regeneration was observed by transmission electron microscope. Uneven and thin epithelial basement membrane, light density of hemidesmosomes, and edematous collagen fibril bundles are shown in the alkali-burned cornea. Injured epithelial basement membrane and hemidesmosomes and edematous collagen fibril bundles resulting from alkali-burned mouse cornea was repaired by bevacizumab treatment. This study demonstrates that bevacizumab can play an important role in wound healing in the cornea by accelerating the reestablishment of basement membrane integrity that leads to barriers for scar formation.

  18. Accelerated nervous system development contributes to behavioral efficiency in the laboratory mouse: a behavioral review and theoretical proposal.

    PubMed

    Whishaw, I Q; Metz, G A; Kolb, B; Pellis, S M

    2001-11-01

    The emergence of the laboratory mouse as a favored species for genetic research has posed a number of problems for scientists interested in the reflection of genetic influences in mouse behavior. It is commonly thought that rat behavior, which has been studied more extensively than mouse behavior, could be easily generalized to mice. In this article, a number of categories of behavior displayed by the mouse (motor, spatial, defensive, social) are reviewed and contrasted with the same categories of behavior displayed by the rat. The comparison suggests that mouse behavior is simpler and more dependent upon elementary actions than the behavior of the rat. We suggest that the behavioral simplification in the mouse adapts it for a different ecological niche than that occupied by the rat. We propose that this simplification may be mediated by accelerated brain maturation during development. We further propose that this developmental acceleration in the mouse renders it less dependent upon complex social behavior and plastic nervous system changes associated with learning than the rat. This difference poses problems for the development of relevant methods of behavioral analysis and interpretation. Since the mouse's biological adaptations will be reflected in laboratory behavior, suggestions are made for behavioral approaches to the study and interpretation of mouse behavior.

  19. HSP70i Accelerates Depigmentation in a Mouse Model of Autoimmune Vitiligo

    PubMed Central

    Denman, Cecele J.; McCracken, James; Hariharan, Vidhya; Klarquist, Jared; Oyarbide-Valencia, Kepa; Guevara-Patiño, José A.; Le Poole, I. Caroline

    2013-01-01

    Vitiligo is a T-cell-mediated autoimmune disease of the skin. Progressive depigmentation accelerates in response to stress. Personal trauma, contact with bleaching phenols, overexposure to UV, and mechanical injury can lead to progressive loss of melanocytes. This study was focused on the role of stress protein heat shock protein (HSP)70 for translating stress into an autoimmune disease to melanocytes. Intracellular HSP70 can act as a cytoprotectant, preventing apoptosis in cells under stress. Isoform HSP70i can be secreted by live cells, and in prior in vitro studies, HSP70 has been shown to activate dendritic cells and elicit an immune response to chaperoned proteins and peptides. Here, the role of HSP70 in precipitating and perpetuating vitiligo was assessed in vivo in a mouse model of autoimmune vitiligo. In this model, depigmentation was introduced by gene gun vaccination with eukaryotic expression plasmids encoding melanocyte differentiation antigens. Inclusion of human and mouse-derived inducible HSP70 in the vaccination protocol significantly increased and accelerated depigmentation in this model, accompanied by the induction of prolonged humoral responses to HSP70. Cytotoxicity toward targets loaded with a K(b)-restricted tyrosinase-related protein 2-derived peptide correlated with depigmentation. The data presented strongly support a role for HSP70i in progressive depigmentation in vivo. PMID:18337834

  20. Recombinant Human Epidermal Growth Factor Accelerates Recovery of Mouse Small Intestinal Mucosa After Radiation Damage

    SciTech Connect

    Lee, Kang Kyoo; Jo, Hyang Jeong; Hong, Joon Pio; Lee, Sang-wook Sohn, Jung Sook; Moon, Soo Young; Yang, Sei Hoon; Shim, Hyeok; Lee, Sang Ho; Ryu, Seung-Hee; Moon, Sun Rock

    2008-07-15

    Purpose: To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation. Methods and Materials: A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate. Results: The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups. Conclusions: Systemic administration of rhEGF accelerates recovery from mucosal damage induced by irradiation. We suggest that rhEGF treatment shows promise for the reduction of small intestinal damage after irradiation.

  1. Effect of an Enhanced Nose-to-Brain Delivery of Insulin on Mild and Progressive Memory Loss in the Senescence-Accelerated Mouse.

    PubMed

    Kamei, Noriyasu; Tanaka, Misa; Choi, Hayoung; Okada, Nobuyuki; Ikeda, Takamasa; Itokazu, Rei; Takeda-Morishita, Mariko

    2017-03-06

    Insulin is now considered to be a new drug candidate for treating dementias, such as Alzheimer's disease, whose pathologies are linked to insulin resistance in the brain. Our recent work has clarified that a noncovalent strategy involving cell-penetrating peptides (CPPs) can increase the direct transport of insulin from the nasal cavity into the brain parenchyma. The present study aimed to determine whether the brain insulin level increased by intranasal coadministration of insulin with the CPP penetratin has potential for treating dementia. The pharmacological actions of insulin were investigated at different stages of memory impairment using a senescence-accelerated mouse-prone 8 (SAMP8) model. The results of spatial learning tests suggested that chronic intranasal administration of insulin with l-penetratin to SAMP8 slowed the progression of memory loss in the early stage of memory impairment. However, contrary to expectations, this strategy using penetratin was ineffective in recovering the severe cognitive dysfunction in the progressive stage, which involves brain accumulation of amyloid β (Aβ). Immunohistological examination of hippocampal regions of samples from SAMP8 in the progressive stage suggested that accelerated nose-to-brain insulin delivery had a partial neuroprotective function but unexpectedly increased Aβ plaque deposition in the hippocampus. These findings suggest that the efficient nose-to-brain delivery of insulin combined with noncovalent CPP strategy has different effects on dementia during the mild and progressive stages of cognitive dysfunction.

  2. Splicing-directed therapy in a new mouse model of human accelerated aging.

    PubMed

    Osorio, Fernando G; Navarro, Claire L; Cadiñanos, Juan; López-Mejía, Isabel C; Quirós, Pedro M; Bartoli, Catherine; Rivera, José; Tazi, Jamal; Guzmán, Gabriela; Varela, Ignacio; Depetris, Danielle; de Carlos, Félix; Cobo, Juan; Andrés, Vicente; De Sandre-Giovannoli, Annachiara; Freije, José M P; Lévy, Nicolas; López-Otín, Carlos

    2011-10-26

    Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent development of the first therapeutic approaches for this disease. However, none of these earlier works have addressed the aberrant and pathogenic LMNA splicing observed in HGPS patients because of the lack of an appropriate mouse model. Here, we report a genetically modified mouse strain that carries the HGPS mutation. These mice accumulate progerin, present histological and transcriptional alterations characteristic of progeroid models, and phenocopy the main clinical manifestations of human HGPS, including shortened life span and bone and cardiovascular aberrations. Using this animal model, we have developed an antisense morpholino-based therapy that prevents the pathogenic Lmna splicing, markedly reducing the accumulation of progerin and its associated nuclear defects. Treatment of mutant mice with these morpholinos led to a marked amelioration of their progeroid phenotype and substantially extended their life span, supporting the effectiveness of antisense oligonucleotide-based therapies for treating human diseases of accelerated aging.

  3. Accelerated renal disease is associated with the development of metabolic syndrome in a glucolipotoxic mouse model

    PubMed Central

    Martínez-García, Cristina; Izquierdo, Adriana; Velagapudi, Vidya; Vivas, Yurena; Velasco, Ismael; Campbell, Mark; Burling, Keith; Cava, Fernando; Ros, Manuel; Orešič, Matej; Vidal-Puig, Antonio; Medina-Gomez, Gema

    2012-01-01

    SUMMARY Individuals with metabolic syndrome are at high risk of developing chronic kidney disease (CKD) through unclear pathogenic mechanisms. Obesity and diabetes are known to induce glucolipotoxic effects in metabolically relevant organs. However, the pathogenic role of glucolipotoxicity in the aetiology of diabetic nephropathy is debated. We generated a murine model, the POKO mouse, obtained by crossing the peroxisome proliferator-activated receptor gamma 2 (PPARγ2) knockout (KO) mouse into a genetically obese ob/ob background. We have previously shown that the POKO mice showed: hyperphagia, insulin resistance, hyperglycaemia and dyslipidaemia as early as 4 weeks of age, and developed a complete loss of normal β-cell function by 16 weeks of age. Metabolic phenotyping of the POKO model has led to investigation of the structural and functional changes in the kidney and changes in blood pressure in these mice. Here we demonstrate that the POKO mouse is a model of renal disease that is accelerated by high levels of glucose and lipid accumulation. Similar to ob/ob mice, at 4 weeks of age these animals exhibited an increased urinary albumin:creatinine ratio and significantly increased blood pressure, but in contrast showed a significant increase in the renal hypertrophy index and an associated increase in p27Kip1 expression compared with their obese littermates. Moreover, at 4 weeks of age POKO mice showed insulin resistance, an alteration of lipid metabolism and glomeruli damage associated with increased transforming growth factor beta (TGFβ) and parathyroid hormone-related protein (PTHrP) expression. At this age, levels of proinflammatory molecules, such as monocyte chemoattractant protein-1 (MCP-1), and fibrotic factors were also increased at the glomerular level compared with levels in ob/ob mice. At 12 weeks of age, renal damage was fully established. These data suggest an accelerated lesion through glucolipotoxic effects in the renal pathogenesis in POKO mice

  4. Size of lethality target in mouse immature oocytes determined with accelerated heavy ions.

    PubMed

    Straume, T; Dobson, R L; Kwan, T C

    1989-01-01

    Mouse immature oocytes were irradiated in vivo with highly charged, heavy ions from the Bevalac accelerator at the Lawrence Berkeley Laboratory. The particles used were 670-MeV/nucleon Si14+, 570-MeV/nucleon Ar18+, and 450-MeV/nucleon Fe26+. The cross-sectional area of the lethality target in these extremely radiosensitive cells was determined from fluence-response curves and information on energy deposition by delta rays. Results indicate a target cross-section larger than that of the nucleus, one which closely approximates the cross-sectional area of the entire oocyte. For 450-MeV/nucleon Fe26+ particles, the predicted target cross-sectional area is 120 +/- 16 microns2, comparing well with the microscopically determined cross-sectional area of 111 +/- 12 microns2 for these cells. The present results are in agreement with our previous target studies which implicate the oocyte plasma membrane.

  5. Accelerated microglial pathology is associated with Aβ plaques in mouse models of Alzheimer’s disease

    PubMed Central

    Baron, Rona; Babcock, Alicia A; Nemirovsky, Anna; Finsen, Bente; Monsonego, Alon

    2014-01-01

    Microglia integrate within the neural tissue with a distinct ramified morphology through which they scan the surrounding neuronal network. Here, we used a digital tool for the quantitative morphometric characterization of fine cortical microglial structures in mice, and the changes they undergo with aging and in Alzheimer’s-like disease. We show that, compared with microglia in young mice, microglia in old mice are less ramified and possess fewer branches and fine processes along with a slightly increased proinflammatory cytokine expression. A similar microglial pathology appeared 6–12 months earlier in mouse models of Alzheimer’s disease (AD), along with a significant increase in brain parenchyma lacking coverage by microglial processes. We further demonstrate that microglia near amyloid plaques acquire unique activated phenotypes with impaired process complexity. We thus show that along with a chronic proinflammatory reaction in the brain, aging causes a significant reduction in the capacity of microglia to scan their environment. This type of pathology is markedly accelerated in mouse models of AD, resulting in a severe microglial process deficiency, and possibly contributing to enhanced cognitive decline. PMID:24641683

  6. Accelerated Human Mutant Tau Aggregation by Knocking Out Murine Tau in a Transgenic Mouse Model

    PubMed Central

    Ando, Kunie; Leroy, Karelle; Héraud, Céline; Yilmaz, Zehra; Authelet, Michèle; Suain, Valèrie; De Decker, Robert; Brion, Jean-Pierre

    2011-01-01

    Many models of human tauopathies have been generated in mice by expression of a human mutant tau with maintained expression of mouse endogenous tau. Because murine tau might interfere with the toxic effects of human mutant tau, we generated a model in which a pathogenic human tau protein is expressed in the absence of wild-type tau protein, with the aim of facilitating the study of the pathogenic role of the mutant tau and to reproduce more faithfully a human tauopathy. The Tg30 line is a tau transgenic mouse model overexpressing human 1N4R double-mutant tau (P301S and G272V) that develops Alzheimer's disease-like neurofibrillary tangles in an age-dependent manner. By crossing Tg30 mice with mice invalidated for their endogenous tau gene, we obtained Tg30xtau−/− mice that express only exogenous human double-mutant 1N4R tau. Although Tg30xtau−/− mice express less tau protein compared with Tg30, they exhibit signs of decreased survival, increased proportion of sarkosyl-insoluble tau in the brain and in the spinal cord, increased number of Gallyas-positive neurofibrillary tangles in the hippocampus, increased number of inclusions in the spinal cord, and a more severe motor phenotype. Deletion of murine tau accelerated tau aggregation during aging of this mutant tau transgenic model, suggesting that murine tau could interfere with the development of tau pathology in transgenic models of human tauopathies. PMID:21281813

  7. Dysfunctional Transforming Growth Factor-β Receptor II Accelerates Prostate Tumorigenesis in the TRAMP Mouse Model

    PubMed Central

    Pu, Hong; Collazo, Joanne; Jones, Elisabeth; Gayheart, Dustin; Sakamoto, Shinichi; Vogt, Adam; Mitchell, Bonnie; Kyprianou, Natasha

    2009-01-01

    The contribution of a dysfunctional TGF-β type II receptor (TGFβRII) to prostate cancer initiation and progression was investigated in an in vivo mouse model. Transgenic mice harboring the dominant-negative mutant TGF-β type II receptor (DNTGFβRII) in mouse epithelial cell were crossed with the TRAMP prostate cancer transgenic mouse to characterize the in vivo consequences of inactivated TGF-β signaling on prostate tumor initiation and progression. Histopathological diagnosis of prostate specimens from the TRAMP+/DNTGFβRII double transgenic mice, revealed the appearance of early malignant changes and subsequently highly aggressive prostate tumors at a younger age, compared to littermates TRAMP+/Wt TGFβRII mice. Immunohistochemical and western blotting analysis revealed significantly increased proliferative and apoptotic activities, as well as vascularity and macrophage infiltration that correlated with an elevated VEGF and MCP-1 protein levels in prostates from TRAMP+/DNTGFβRII+ mice. An epithelial-mesenchymal transition (EMT)-effect was also detected in prostates of TRAMP+/DNTGFβRII mice, as documented by the loss of epithelial markers (E-cadherin and β-catenin) and upregulation of mesenchymal markers (N-cadherin) and EMT-transcription factor Snail. A significant increase in the androgen receptor (AR) mRNA and protein levels was associated with the early onset of prostate tumorigenesis in TRAMP+/DNTGFβRII mice. Our results indicate that in vivo disruption of TGF-β signaling accelerates the pathological malignant changes in the prostate by altering the kinetics of prostate growth and inducing EMT. The study also suggests that a dysfunctional TGFβRII augments AR expression and promotes inflammation in early stage tumor growth thus conferring a significant contribution by TGF-β to prostate cancer progression. PMID:19738062

  8. Reduction of Synaptojanin 1 Accelerates Aβ Clearance and Attenuates Cognitive Deterioration in an Alzheimer Mouse Model*

    PubMed Central

    Zhu, Li; Zhong, Minghao; Zhao, Jiaying; Rhee, Hannah; Caesar, Ina; Knight, Elysse M.; Volpicelli-Daley, Laura; Bustos, Victor; Netzer, William; Liu, Lijuan; Lucast, Louise; Ehrlich, Michelle E.; Robakis, Nikolaos K.; Gandy, Samuel E.; Cai, Dongming

    2013-01-01

    Recent studies link synaptojanin 1 (synj1), the main phosphoinositol (4,5)-biphosphate phosphatase (PI(4,5)P2-degrading enzyme) in the brain and synapses, to Alzheimer disease. Here we report a novel mechanism by which synj1 reversely regulates cellular clearance of amyloid-β (Aβ). Genetic down-regulation of synj1 reduces both extracellular and intracellular Aβ levels in N2a cells stably expressing the Swedish mutant of amyloid precursor protein (APP). Moreover, synj1 haploinsufficiency in an Alzheimer disease transgenic mouse model expressing the Swedish mutant APP and the presenilin-1 mutant ΔE9 reduces amyloid plaque load, as well as Aβ40 and Aβ42 levels in hippocampus of 9-month-old animals. Reduced expression of synj1 attenuates cognitive deficits in these transgenic mice. However, reduction of synj1 does not affect levels of full-length APP and the C-terminal fragment, suggesting that Aβ generation by β- and γ-secretase cleavage is not affected. Instead, synj1 knockdown increases Aβ uptake and cellular degradation through accelerated delivery to lysosomes. These effects are partially dependent upon elevated PI(4,5)P2 with synj1 down-regulation. In summary, our data suggest a novel mechanism by which reduction of a PI(4,5)P2-degrading enzyme, synj1, improves amyloid-induced neuropathology and behavior deficits through accelerating cellular Aβ clearance. PMID:24052255

  9. The GLP-1 Receptor Agonist Liraglutide Improves Memory Function and Increases Hippocampal CA1 Neuronal Numbers in a Senescence-Accelerated Mouse Model of Alzheimer's Disease.

    PubMed

    Hansen, Henrik H; Fabricius, Katrine; Barkholt, Pernille; Niehoff, Michael L; Morley, John E; Jelsing, Jacob; Pyke, Charles; Knudsen, Lotte Bjerre; Farr, Susan A; Vrang, Niels

    2015-01-01

    Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor agonists, currently used in the management of type 2 diabetes, exhibit neurotrophic and neuroprotective effects in amyloid-β (Aβ) toxicity models of Alzheimer's disease (AD). We investigated the potential pro-cognitive and neuroprotective effects of the once-daily GLP-1 receptor agonist liraglutide in senescence-accelerated mouse prone 8 (SAMP8) mice, a model of age-related sporadic AD not dominated by amyloid plaques. Six-month-old SAMP8 mice received liraglutide (100 or 500 μg/kg/day, s.c.) or vehicle once daily for 4 months. Vehicle-dosed age-matched 50% back-crossed as well as untreated young (4-month-old) SAMP8 mice were used as control groups for normal memory function. Vehicle-dosed 10-month-old SAMP8 mice showed significant learning and memory retention deficits in an active-avoidance T-maze, as compared to both control groups. Also, 10-month-old SAMP8 mice displayed no immunohistological signatures of amyloid-β plaques or hyperphosphorylated tau, indicating the onset of cognitive deficits prior to deposition of amyloid plaques and neurofibrillary tangles in this AD model. Liraglutide significantly increased memory retention and total hippocampal CA1 pyramidal neuron numbers in SAMP8 mice, as compared to age-matched vehicle-dosed SAMP8 mice. In conclusion, liraglutide delayed or partially halted the progressive decline in memory function associated with hippocampal neuronal loss in a mouse model of pathological aging with characteristics of neurobehavioral and neuropathological impairments observed in early-stage sporadic AD.

  10. Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis.

    PubMed

    Hlady, Ryan A; Novakova, Slavomira; Opavska, Jana; Klinkebiel, David; Peters, Staci L; Bies, Juraj; Hannah, Jay; Iqbal, Javeed; Anderson, Kristi M; Siebler, Hollie M; Smith, Lynette M; Greiner, Timothy C; Bastola, Dhundy; Joshi, Shantaram; Lockridge, Oksana; Simpson, Melanie A; Felsher, Dean W; Wagner, Kay-Uwe; Chan, Wing C; Christman, Judith K; Opavsky, Rene

    2012-01-01

    DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals. DNA methylation contributes to the epigenetic control of gene transcription and is deregulated in virtually all human tumors. To better understand the generation of cancer-specific methylation patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T cells accelerated lymphomagenesis by increasing cellular proliferation, which suggests that Dnmt3b functions as a tumor suppressor. Global methylation profiling revealed numerous gene promoters as potential targets of Dnmt3b activity, the majority of which were demethylated in Dnmt3b-/- lymphomas, but not in Dnmt3b-/- pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine methylation in cancer. Functional analysis identified the gene Gm128 (which we termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b activity. We found that Ment was gradually demethylated and overexpressed during tumor progression in Dnmt3b-/- lymphomas. Similarly, MENT was overexpressed in 67% of human lymphomas, and its transcription inversely correlated with methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells with a proliferative advantage. Our findings identify Ment as an enhancer of lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and suggest it could be a potential target for anticancer therapies.

  11. Multiplex Chromosomal Exome Sequencing Accelerates Identification of ENU-Induced Mutations in the Mouse.

    PubMed

    Sun, Miao; Mondal, Kajari; Patel, Viren; Horner, Vanessa L; Long, Alyssa B; Cutler, David J; Caspary, Tamara; Zwick, Michael E

    2012-01-01

    Forward genetic screens in Mus musculus have proved powerfully informative by revealing unsuspected mechanisms governing basic biological processes. This approach uses potent chemical mutagens, such as N-ethyl-N-nitrosourea (ENU), to randomly induce mutations in mice, which are then bred and phenotypically screened to identify lines that disrupt a specific biological process of interest. Although identifying a mutation using the rich resources of mouse genetics is straightforward, it is unfortunately neither fast nor cheap. Here we show that detecting newly induced causal variants in a forward genetic screen can be accelerated dramatically using a methodology that combines multiplex chromosome-specific exome capture, next-generation sequencing, rapid mapping, sequence annotation, and variation filtering. The key innovation of our method is multiplex capture and sequence that allows the simultaneous survey of both mutant, parental, and background strains in a single experiment. By comparing variants identified in mutant offspring with those found in dbSNP, the unmutagenized background strains, and parental lines, induced causative mutations can be distinguished immediately from preexisting variation or experimental artifact. Here we demonstrate this approach to find the causative mutations induced in four novel ENU lines identified from a recent ENU screen. In all four cases, after applying our method, we found six or fewer putative mutations (and sometimes only a single one). Determining the causative variant was then easily achieved through standard segregation approaches. We have developed this process into a community resource that will speed up individual labs' ability to identify the genetic lesion in mutant mouse lines; all of our reagents and software tools are open source and available to the broader scientific community.

  12. Loss of CDH1 and Pten accelerates cellular invasiveness and angiogenesis in the mouse uterus.

    PubMed

    Lindberg, Mallory E; Stodden, Genna R; King, Mandy L; MacLean, James A; Mann, Jordan L; DeMayo, Francesco J; Lydon, John P; Hayashi, Kanako

    2013-07-01

    E-cadherin (CDH1) is a cell adhesion molecule that coordinates key morphogenetic processes regulating cell growth, cell proliferation, and apoptosis. Loss of CDH1 is a trademark of the cellular event epithelial to mesenchymal transition, which increases the metastatic potential of malignant cells. PTEN is a tumor-suppressor gene commonly mutated in many human cancers, including endometrial cancer. In the mouse uterus, ablation of Pten induces epithelial hyperplasia, leading to endometrial carcinomas. However, loss of Pten alone does not affect longevity until around 5 mo. Similarly, conditional ablation of Cdh1 alone does not predispose mice to cancer. In this study, we characterized the impact of dual Cdh1 and Pten ablation (Cdh1(d/d) Pten(d/d)) in the mouse uterus. We observed that Cdh1(d/d) Pten(d/d) mice died at Postnatal Days 15-19 with massive blood loss. Their uteri were abnormally structured with curly horns, disorganized epithelial structure, and increased cell proliferation. Co-immunostaining of KRT8 and ACTA2 showed invasion of epithelial cells into the myometrium. Further, the uteri of Cdh1(d/d) Pten(d/d) mice had prevalent vascularization in both the endometrium and myometrium. We also observed reduced expression of estrogen and progesterone receptors, loss of cell adherens, and tight junction molecules (CTNNB1 and claudin), as well as activation of AKT in the uteri of Cdh1(d/d) Pten(d/d) mice. However, complex hyperplasia was not found in the uteri of Cdh1(d/d) Pten(d/d) mice. Collectively, these findings suggest that ablation of Pten with Cdh1 in the uterus accelerates cellular invasiveness and angiogenesis and causes early death.

  13. Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II.

    PubMed

    Nakagawa, Takashi; Hasegawa, Yu; Uekawa, Ken; Kim-Mitsuyama, Shokei

    2017-01-01

    Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairment in Alzheimer's disease (AD), focusing on angiotensin II. (1) CKD was induced in 5XFAD mice, an AD model mouse, and wild-type mice by feeding an adenine-containing diet and the effect on cognitive function was compared between both strains. There was no significant difference regarding the severity of CKD induced by adenine between the strains. In 5XFAD mice, the CKD group exhibited significant cognitive impairment while the control group (control diet-fed group) did not, as evidenced by a passive avoidance test. On the other hand, in wild-type mice, neither the CKD group nor the control group showed cognitive impairment. Thus, CKD itself appears to accelerate cognitive impairment in AD mice. (2) We also examined the effect of olmesartan, an angiotensin II receptor blocker, on 5XFAD mice with CKD to elucidate the potential involvement of angiotensin II. As evidenced by the findings of the water maze test, olmesartan treatment significantly ameliorated the impairment of spatial learning and memory function induced by CKD in 5XFAD mice. Olmesartan treatment significantly ameliorated blood-brain barrier (BBB) disruption induced by CKD in 5XFAD mice. Furthermore, olmesartan reduced hippocampal oxidative stress in 5XFAD with CKD to similar levels to the control group of 5XFAD fed standard diet. Hence, the amelioration of CKD-induced cognitive impairment in 5XFAD mice by olmesartan appears to be mediated by the suppression of BBB disruption or oxidative stress. In conclusion, we obtained the evidence suggesting that CKD itself accelerates cognitive impairment in AD mice, through angiotensin II. Thus, our work provides a novel insight into the underlying mechanism of the link

  14. Activin A accelerates the progression of fetal oocytes throughout meiosis and early oogenesis in the mouse.

    PubMed

    Liang, Gui-Jin; Zhang, Xi-Feng; Wang, Jun-Jie; Sun, Yuan-Chao; Sun, Xiao-Feng; Cheng, Shun-Feng; Li, Lan; De Felici, Massimo; Shen, Wei

    2015-10-15

    Activins can exert several roles in ovary development. However, little is known about their involvement in early mammalian oogenesis. In this study, we reported that activin receptors (including ActRIA, ActRIB, ActRIIA, and ActRIIB) are expressed throughout the development of the mouse ovaries from 12.5 days postcoitum (dpc) to 21 days postparturition (dpp). Moreover, we found that in vitro, the addition of activin A (ActA) to the culture medium of 12.5 dpc ovarian tissues accelerated the progression of oocytes throughout meiotic prophase I stages. This result was reproduced in vivo following administration of ActA to pregnant mice. The in vitro effect of ActA was associated with increased expression of premeiotic and meiotic genes (including Dazl, Spo11, Stra8, Scp3, and Rec8) in the ovarian tissues. Mechanistically, ActA-dependent SMAD3 signaling modulated the expression of members of the retinoic acid (RA) system, including the RA degradation CYP26B1 enzyme and the RA receptors. Finally, ActA promoted the survival and growth of fetal and early postnatal oocytes and primordial follicle assembly both in vitro and in vivo. In conclusion, the present study identifies new roles of ActA in early oogenesis and suggested that ActA and RA might cooperate in promoting meiosis in female germ cells.

  15. Hypertension accelerates the progression of Alzheimer-like pathology in a mouse model of the disease.

    PubMed

    Cifuentes, Diana; Poittevin, Marine; Dere, Ekrem; Broquères-You, Dong; Bonnin, Philippe; Benessiano, Joëlle; Pocard, Marc; Mariani, Jean; Kubis, Nathalie; Merkulova-Rainon, Tatyana; Lévy, Bernard I

    2015-01-01

    Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm(2); P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 34%, and 33%, respectively, compared with wild-type mice; P<0.05). Our results indicate that hypertension accelerates the development of Alzheimer disease-related structural and functional alterations, partially through cerebral vasculature impairment and reduced nitric oxide production.

  16. Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing

    PubMed Central

    Hsu, I; Parkinson, L G; Shen, Y; Toro, A; Brown, T; Zhao, H; Bleackley, R C; Granville, D J

    2014-01-01

    Chronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition. PMID:25299783

  17. Absence of AMPKα2 accelerates cellular senescence via p16 induction in mouse embryonic fibroblasts.

    PubMed

    Ding, Ye; Chen, Jie; Okon, Imoh Sunday; Zou, Ming-Hui; Song, Ping

    2016-02-01

    Emerging evidence suggests that activation of adenosine monophosphate-activated protein kinase (AMPK), an energy gauge and redox sensor, delays aging process. However, the molecular mechanisms by which AMPKα isoform regulates cellular senescence remain largely unknown. The aim of this study was to determine if AMPKα deletion contributes to the accelerated cell senescence by inducing p16(INK4A) (p16) expression thereby arresting cell cycle. The markers of cellular senescence, cell cycle proteins, and reactive oxygen species (ROS) were monitored in cultured mouse embryonic fibroblasts (MEFs) isolated from wild type (WT, C57BL/6J), AMPKα1, or AMPKα2 homozygous deficient (AMPKα1(-/-), AMPKα2(-/-)) mice by Western blot and cellular immunofluorescence staining, as well as immunohistochemistry (IHC) in skin tissue of young and aged mice. Deletion of AMPKα2, the minor isoform of AMPKα, but not AMPKα1 in high-passaged MEFs led to spontaneous cell senescence demonstrated by accumulation of senescence-associated-β-galactosidase (SA-β-gal) staining and foci formation of heterochromatin protein 1 homolog gamma (HP1γ). It was shown here that AMPKα2 deletion upregulates cyclin-dependent kinase (CDK) inhibitor, p16, which arrests cell cycle. Furthermore, AMPKα2 null cells exhibited elevated ROS production. Interestingly, knockdown of HMG box-containing protein 1 (HBP1) partially blocked the cellular senescence of AMPKα2-deleted MEFs via the reduction of p16. Finally, dermal cells senescence, including fibroblasts senescence evidenced by the staining of p16, HBP1, and Ki-67, in the skin of aged AMPKα2(-/-) mice was enhanced when compared with that in wild type mice. Taken together, our results suggest that AMPKα2 isoform plays a fundamental role in anti-oxidant stress and anti-senescence.

  18. Marked Acceleration of Atherosclerosis following Lactobacillus casei induced Coronary Arteritis in a Mouse Model of Kawasaki Disease

    PubMed Central

    Chen, Shuang; Lee, Young Ho; Crother, Timothy R.; Fishbein, Michael; Zhang, Wenxuan; Yilmaz, Atilla; Shimada, Kenichi; Schulte, Danica J; Lehman, Thomas J.A.; Shah, Prediman K.; Arditi, Moshe

    2012-01-01

    Objective To investigate if Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki Disease (KD) accelerates atherosclerosis in hypercholesterolemic mice. Method and Resuslts Apoe−/− or Ldlr−/− mice were injected with LCWE (KD mice) or PBS, fed high fat diet for 8 weeks, and atherosclerotic lesions in aortic sinuses (AS), arch (AC) and whole aorta were assessed. KD mice had larger, more complex aortic lesions with abundant collagen, and both extracellular and intracellular lipid and foam cells, compared to lesions in control mice despite similar cholesterol levels. Both Apoe−/− KD and Ldlr−/− KD mice showed dramatic acceleration in atherosclerosis vs. controls, with increases in en face aortic atherosclerosis and plaque size in both the AS and AC plaques. Accelerated atherosclerosis was associated with increased circulating IL-12p40, IFN-γ, TNF-α, and increased macrophage, DC, and T cell recruitment in lesions. Furthermore, daily injections of the IL-1Ra, which inhibits LCWE induced KD vasculitis, prevented the acceleration of atherosclerosis. Conclusions Our results suggest an important pathophysiologic link between coronary arteritis/vasculitis in the KD mouse model and subsequent atherosclerotic acceleration, supporting the concept that a similar relation may also be present in KD patients. These results also suggest that KD in childhood may predispose to accelerated and early atherosclerosis as adults. PMID:22628430

  19. Novel frame-shift mutation in Slc5a2 encoding SGLT2 in a strain of senescence-accelerated mouse SAMP10.

    PubMed

    Unno, Keiko; Yamamoto, Hiroyuki; Toda, Masateru; Hagiwara, Shiori; Iguchi, Kazuaki; Hoshino, Minoru; Takabayashi, Fumiyo; Hasegawa-Ishii, Sanae; Shimada, Atsuyoshi; Hosokawa, Masanori; Higuchi, Keiichi; Mori, Masayuki

    2014-11-07

    The senescence-accelerated mouse prone10 (SAMP10) strain, a model of aging, exhibits cognitive impairments and cerebral atrophy. We noticed that SAMP10/TaSlc mice, a SAMP10 substrain, have developed persistent glucosuria over the past few years. In the present study, we characterized SAMP10/TaSlc mice and further identified a spontaneous mutation in the Slc5a2 gene encoding sodium-glucose co-transporter (SGLT) 2. The mean concentration of urine glucose was high in SAMP10/TaSlc mice and increased further with advancing age, whereas other strains of senescence-accelerated mice, including SAMP1/SkuSlc, SAMP6/TaSlc and SAMP8/TaSlc or normal aging control SAMR1/TaSlc mice, exhibited no detectable glucose in urine. SAMP10/TaSlc mice consumed increasing amounts of food and water compared to SAMR1/TaSlc mice, suggesting the compensation of polyuria and the loss of glucose. Oral glucose tolerance tests showed decreased glucose reabsorption in the kidney of SAMP10/TaSlc mice. In addition, blood glucose levels decreased in an age-dependent fashion. The kidney was innately larger than that of control mice with no histological alterations. We examined the expression levels of glucose transporters in the kidney. Among SGLT1, SGLT2, glucose transporter (GLUT) 1 and GLUT2, we found a significant decrease only in the level of SGLT2. DNA sequencing of SGLT2 in SAMP10/TaSlc mice revealed a single nucleotide deletion of guanine at 1236, which resulted in a frameshift mutation that produced a truncated protein. We designate this strain as SAMP10/TaSlc-Slc5a2(slc) (SAMP10-ΔSglt2). Recently, SGLT2 inhibitors have been demonstrated to be effective for the treatment of patients with type 2 diabetes (T2D). SAMP10-ΔSglt2 mice may serve as a unique preclinical model to study the link between aging-related neurodegenerative disorders and T2D.

  20. Humanized mouse as an appropriate model for accelerated global HIV research and vaccine development: current trend.

    PubMed

    Ibeh, Bartholomew Okechukwu; Furuta, Yasuhide; Habu, Josiah Bitrus; Ogbadu, Lucy

    2016-09-23

    Humanized mouse models currently have seen improved development and have received wide applications. Its usefulness is observed in cell and tissue transplant involving basic and applied human disease research. In this article, the development of a new generation of humanized mice was discussed as well as their relevant application in HIV disease. Furthermore, current techniques employed to overcome the initial limitations of mouse model were reviewed. Highly immunodeficient mice which support cell and tissue differentiation and do not reject xenografts are indispensable for generating additional appropriate models useful in disease study, this phenomenom deserves emphases, scientific highlight and a definitive research focus. Since the early 2000s, a series of immunodeficient mice appropriate for generating humanized mice has been successively developed by introducing the IL-2Rγ(null) gene (e.g. NOD/SCID/γc(null) and Rag2(null)γc(null) mice) through various genomic approaches. These mice were generated by genetically introducing human cytokine genes into NOD/SCID/γc(null) and Rag2(null)γc(null) mouse backgrounds. The application of these techniques serves as a quick and appropriate mechanistic model for basic and therapeutic investigations of known and emerging infections.

  1. STAT3 accelerates uterine epithelial regeneration in a mouse model of decellularized uterine matrix transplantation

    PubMed Central

    Hiraoka, Takehiro; Saito-Fujita, Tomoko; Matsuo, Mitsunori; Egashira, Mahiro; Matsumoto, Leona; Haraguchi, Hirofumi; Dey, Sudhansu K.; Furukawa, Katsuko S.; Fujii, Tomoyuki; Osuga, Yutaka

    2016-01-01

    Although a close connection between uterine regeneration and successful pregnancy in both humans and mice has been consistently observed, its molecular basis remains unclear. We here established a mouse model of decellularized uterine matrix (DUM) transplantation. Resected mouse uteri were processed with SDS to make DUMs without any intact cells. DUMs were transplanted into the mouse uteri with artificially induced defects, and all the uterine layers were recovered at the DUM transplantation sites within a month. In the regenerated uteri, normal hormone responsiveness in early pregnancy was observed, suggesting the regeneration of functional uteri. Uterine epithelial cells rapidly migrated and formed a normal uterine epithelial layer within a week, indicating a robust epithelial-regenerating capacity. Stromal and myometrial regeneration occurred following epithelial regeneration. In ovariectomized mice, uterine regeneration of the DUM transplantation was similarly observed, suggesting that ovarian hormones are not essential for this regeneration process. Importantly, the regenerating epithelium around the DUM demonstrated heightened STAT3 phosphorylation and cell proliferation, which was suppressed in uteri of Stat3 conditional knockout mice. These data suggest a key role of STAT3 in the initial step of the uterine regeneration process. The DUM transplantation model is a powerful tool for uterine regeneration research. PMID:27358915

  2. Tissue distribution of products of the mouse decay-accelerating factor (DAF) genes. Exploitation of a Daf1 knock-out mouse and site-specific monoclonal antibodies.

    PubMed

    Lin, F; Fukuoka, Y; Spicer, A; Ohta, R; Okada, N; Harris, C L; Emancipator, S N; Medof, M E

    2001-10-01

    Decay-accelerating factor (DAF) is a membrane regulator of C3 activation that protects self cells from autologous complement attack. In humans, DAF is uniformly expressed as a glycosylphosphatidylinositol (GPI)-anchored molecule. In mice, both GPI-anchored and transmembrane-anchored DAF proteins are produced, each of which can be derived from two different genes (Daf1 and Daf2). In this report, we describe a Daf1 gene knock-out mouse arising as the first product of a strategy for targeting one or both Daf genes. As part of the work, we characterize recently described monoclonal antibodies against murine DAF protein using deletion mutants synthesized in yeast, and then employ the monoclonal antibodies in conjunction with wild-type and the Daf1 knock-out mice to determine the tissue distribution of the mouse Daf1 and Daf2 gene products. To enhance the immunohistochemical detection of murine DAF protein, we utilized the sensitive tyramide fluorescence method. In wild-type mice, we found strong DAF labelling of glomeruli, airway and gut epithelium, the spleen, vascular endothelium throughout all tissues, and seminiferous tubules of the testis. In Daf1 knock-out mice, DAF labelling was ablated in most tissues, but strong labelling of the testis and splenic dendritic cells remained. In both sites, reverse transcription-polymerase chain reaction analyses identified both GPI and transmembrane forms of Daf2 gene-derived protein. The results have relevance for studies of in vivo murine DAF function and of murine DAF structure.

  3. 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

    PubMed Central

    Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

    2016-01-01

    Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

  4. Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer's disease.

    PubMed

    Kanamaru, Takuya; Kamimura, Naomi; Yokota, Takashi; Iuchi, Katsuya; Nishimaki, Kiyomi; Takami, Shinya; Akashiba, Hiroki; Shitaka, Yoshitsugu; Katsura, Ken-Ichiro; Kimura, Kazumi; Ohta, Shigeo

    2015-02-05

    Oxidative stress is known to play a prominent role in the onset and early stage progression of Alzheimer's disease (AD). For example, protein oxidation and lipid peroxidation levels are increased in patients with mild cognitive impairment. Here, we created a double-transgenic mouse model of AD to explore the pathological and behavioral effects of oxidative stress. Double transgenic (APP/DAL) mice were constructed by crossing Tg2576 (APP) mice, which express a mutant form of human amyloid precursor protein (APP), with DAL mice expressing a dominant-negative mutant of mitochondrial aldehyde dehydrogenase 2 (ALDH2), in which oxidative stress is enhanced. Y-maze and object recognition tests were performed at 3 and 6 months of age to evaluate learning and memory. The accumulation of amyloid plaques, deposition of phosphorylated-tau protein, and number of astrocytes in the brain were assessed histopathologically at 3, 6, 9, and 12-15 months of age. The life span of APP/DAL mice was significantly shorter than that of APP or DAL mice. In addition, they showed accelerated amyloid deposition, tau phosphorylation, and gliosis. Furthermore, these mice showed impaired performance on Y-maze and object recognition tests at 3 months of age. These data suggest that oxidative stress accelerates cognitive dysfunction and pathological insults in the brain. APP/DAL mice could be a useful model for exploring new approaches to AD treatment.

  5. Simultaneous haploinsufficiency of Pten and Trp53 tumor suppressor genes accelerates tumorigenesis in a mouse model of prostate cancer

    PubMed Central

    Couto, Suzana S.; Cao, Mei; Duarte, Paulo C.; Banach-Petrosky, Whitney; Wang, Shunyou; Romanienko, Peter; Wu, Hong; Cardiff, Robert D.; Abate-Shen, Cory; Cunha, Gerald R.

    2010-01-01

    Tumor suppressor gene PTEN is important in the initiation and progression of human prostate carcinoma, whereas the role of TP53 remains controversial. Since Pten/Trp53 double conditional knockout mice show earlier onset and fast progression of prostate cancer when compared to Pten knockout mice, we asked whether heterozygosity of these two tumor suppressor genes was sufficient to accelerate prostatic tumorigenesis. To answer this question we examined prostatic lesion progression of Pten/Trp53 double heterozygous mice and a series of controls such as Pten heterozygous, Pten conditional knockout, Trp53 heterozygous and Trp53 knockout mice. Tissue recombination of adult prostatic epithelium coupled with embryonic rat seminal vesicle mesenchyme was used as a tool to stimulate prostatic epithelial proliferation. In our study, high-grade prostatic intraepithelial neoplasia (PIN) was found with high frequency at 8 weeks post-tissue recombination transplantation. PIN lesions in Pten/Trp53 double heterozygous mice were more severe than those seen in Pten heterozygous alone. Furthermore, morphologic features attributable to Pten or Trp53 loss appeared to be enhanced in double heterozygous tissues. LOH analysis of Pten and Trp53 in genomic DNA collected from high-grade PIN lesions in Pten heterozygous and Pten/Trp53 double heterozygous mice showed an intact wild-type allele for both genes in all samples examined. In conclusion, simultaneous heterozygosity of Pten and Trp53 accelerates prostatic tumorigenesis in this mouse model of prostate cancer independently of loss of heterozygosity of either gene. PMID:19281769

  6. Accelerated maturation of limb mesenchyme by the BrachypodH mouse mutation.

    PubMed

    Owens, E M; Solursh, M

    1983-01-01

    Mesenchyme cell populations prepared from proximal and distal halves of stage 20 mouse forelimb buds are shown to behave under in vitro micromass culture conditions like analogous cell populations obtained from chick embryo limb buds. While the distal cells are spontaneously chondrogenic, the proximal cells make aggregates which are only potentially chondrogenic after treatment with dibutyryl cyclic AMP. In addition, stage 20 mouse whole limb bud cells homozygous for the brachypodismH (bpH) mutation are shown to behave similarly to 'normal' proximal cells. Both make fewer aggregates and nodules and both have faster aggregation rates (determined as the rate of disappearance of single cells over time) in rotation cultures than 'normal' distal or whole limb bud cells. These results support the hypothesis that the bpH mutation specifically decreases the proportion of spontaneously chondrogenic mesenchyme cells (that is, distal-like cells) present at certain developmental stages in the limb bud, resulting in a prematurely high proportion of proximal-like cells.

  7. Pten Inactivation Accelerates Oncogenic K-ras-Initiated Tumorigenesis in a Mouse Model of Lung Cancer

    PubMed Central

    Iwanaga, Kentaro; Yang, Yanan; Raso, Maria Gabriela; Ma, Lijiang; Hanna, Amy E.; Thilaganathan, Nishan; Moghaddam, Seyed; Evans, Christopher M.; Li, Huaiguang; Cai, Wei-Wen; Sato, Mitsuo; Minna, John D.; Wu, Hong; Creighton, Chad J.; Demayo, Francesco J.; Wistuba, Ignacio I.; Kurie, Jonathan M.

    2009-01-01

    Phosphatase and tensin homologue deleted from chromosome 10 (Pten) is expressed aberrantly in non-small cell lung cancer cells, but the role of Pten in lung neoplasia has not been fully elucidated. In this study, we used a genetic approach to inactivate Pten in the bronchial epithelium of mice. Although, by itself, Pten inactivation had no discernible effect on bronchial epithelial histology, it accelerated lung tumorigenesis initiated by oncogenic K-ras, causing more rapid lethality than that induced by oncogenic K-ras alone (8 weeks versus 24 weeks of median duration of survival, respectively). Lung tumors arose in K-ras mutant, Pten-deficient mice that rapidly obstructed bronchial lumina and replaced alveolar spaces. Relative to K-ras mutant tumors, the K-ras mutant, Pten-deficient tumors exhibited more advanced histologic severity and more prominent inflammation and vascularity. Thus, Pten inactivation cooperated with oncogenic K-ras in promoting lung tumorigenesis. PMID:18281487

  8. Acceleration of fusion in mouse palates by in vitro exposure to excess G

    NASA Technical Reports Server (NTRS)

    Duke, J.; Janer, L.; Campbell, M.

    1984-01-01

    Palatal shelves from 13- and 14-day mouse embryos were excised and cultured in contiguous pairs. Experimental cultures were exposed to 2.6 G in a culture centrifuge; controls were in the same incubator. After 24 hours, palates were prepared for light or electron microscopy. Scoring of paraffin sections according to the stage of fusion seen in the medial epithelial edges (MEE) showed that palates exposed to excess G were in more advanced stages of fusion than were controls. Ultrastructurally, control MEE had tightly apposed cell membranes and numerous desmosomes; in centrifuged MEE, desmosomes had been removed and there was much intercellular space. Nuclear membranes were intact in control MEE, but showed marked deterioration in MEE of centrifuged palates. Few lysosomes and no necrosis were seen in control MEE; centrifuged MEE had numerous lysosomes as well as necrotic cells. Basal lamina were intact in controls, but interrupted in centrifuged palates. The results confirm the hypothesis that gravitational increases speed up the differentiative process.

  9. UCP2 overexpression worsens mitochondrial dysfunction and accelerates disease progression in a mouse model of amyotrophic lateral sclerosis.

    PubMed

    Peixoto, Pablo M; Kim, Hyun-Jeong; Sider, Brittany; Starkov, Anatoly; Horvath, Tamas L; Manfredi, Giovanni

    2013-11-01

    Mitochondrial dysfunction leading to deficits in energy production, Ca(2+) uptake capacity, and free radical generation has been implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) caused by mutations in Cu,Zn superoxide dismutase (SOD1). Numerous studies link UCP2, a member of the uncoupling protein family, to protection of neurons from mitochondrial dysfunction and oxidative damage in various mouse models of acute stress and neurodegeneration, including Parkinson's disease. Here, we tested the potential neuroprotective effects of UCP2 and its ability to modulate mitochondrial function, in the G93A mutant SOD1 mouse model of familial ALS. Disease phenotype, mitochondrial bioenergetics, and Ca(2+) uptake capacity were investigated in the central nervous system of double transgenic mice, expressing both human mutant G93A SOD1 and human UCP2 (hUCP2). Unexpectedly, hUCP2 expression accelerated the disease course of SOD1 mutant mice. In addition, we did not observe a classical uncoupling effect of hUCP2 in G93A brain mitochondria, although we did detect a decrease in reactive oxygen species (ROS) production from mitochondria challenged with the respiratory chain inhibitors rotenone and antimycin A. We also found that mitochondrial Ca(2+) uptake capacity was decreased in the double transgenic mice, as compared to G93A mice. In summary, our results indicate that the neuroprotective role of UCP2 in neurodegeneration is disease-specific and that, while a mild uncoupling by UCP2 in brain mitochondria may protect against neurodegeneration in some injury paradigms, the mitochondrial damage and the disease caused by mutant SOD1 cannot be ameliorated by UCP2 overexpression.

  10. Elevated-temperature-induced acceleration of PACT clearing process of mouse brain tissue

    NASA Astrophysics Data System (ADS)

    Yu, Tingting; Qi, Yisong; Zhu, Jingtan; Xu, Jianyi; Gong, Hui; Luo, Qingming; Zhu, Dan

    2017-01-01

    Tissue optical clearing technique shows a great potential for neural imaging with high resolution, especially for connectomics in brain. The passive clarity technique (PACT) is a relative simple clearing method based on incubation, which has a great advantage on tissue transparency, fluorescence preservation and immunostaining compatibility for imaging tissue blocks. However, this method suffers from long processing time. Previous studies indicated that increasing temperature can speed up the clearing. In this work, we aim to systematacially and quantitatively study this influence based on PACT with graded increase of temperatures. We investigated the process of optical clearing of brain tissue block at different temperatures, and found that elevated temperature could accelerate the clearing process and also had influence on the fluorescence intensity. By balancing the advantages with drawbacks, we conclude that 42–47 °C is an alternative temperature range for PACT, which can not only produce faster clearing process, but also retain the original advantages of PACT by preserving endogenous fluorescence well, achieving fine morphology maintenance and immunostaining compatibility.

  11. Elevated-temperature-induced acceleration of PACT clearing process of mouse brain tissue

    PubMed Central

    Yu, Tingting; Qi, Yisong; Zhu, Jingtan; Xu, Jianyi; Gong, Hui; Luo, Qingming; Zhu, Dan

    2017-01-01

    Tissue optical clearing technique shows a great potential for neural imaging with high resolution, especially for connectomics in brain. The passive clarity technique (PACT) is a relative simple clearing method based on incubation, which has a great advantage on tissue transparency, fluorescence preservation and immunostaining compatibility for imaging tissue blocks. However, this method suffers from long processing time. Previous studies indicated that increasing temperature can speed up the clearing. In this work, we aim to systematacially and quantitatively study this influence based on PACT with graded increase of temperatures. We investigated the process of optical clearing of brain tissue block at different temperatures, and found that elevated temperature could accelerate the clearing process and also had influence on the fluorescence intensity. By balancing the advantages with drawbacks, we conclude that 42–47 °C is an alternative temperature range for PACT, which can not only produce faster clearing process, but also retain the original advantages of PACT by preserving endogenous fluorescence well, achieving fine morphology maintenance and immunostaining compatibility. PMID:28139694

  12. Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington’s disease

    PubMed Central

    Potter, Michelle C; Yuan, Chunyan; Ottenritter, Conwell; Mughal, Mohamed; van Praag, Henriette

    2010-01-01

    Exercise benefits both general health and brain function in rodents and humans. However, it is less clear whether physical activity prevents or ameliorates neurodegenerative diseases. The aim of the present study was to determine whether voluntary wheel running can delay the onset or reduce the severity of Huntington’s disease (HD) in a mouse model. To investigate whether running may delay HD symptoms lifespan, disease onset, locomotor activity, glucose levels, weight, striatal volume, inclusions, cognition and hippocampal neurogenesis were studied in male N171-82Q transgenic HD mice. Running started in pre-symptomatic (44±1 days old) male HD mice, did not improve function and appeared to accelerate disease onset. In particular, HD runners had an earlier onset of disease symptoms (shaking, hunched back and poor grooming), reduced striatal volume and impaired motor behavior, including a shorter latency to fall from the rotarod compared to sedentary controls. Furthermore, weight loss, reduced lifespan, hyperglycemia, Morris water maze learning deficits, diminished hippocampal neurogenesis, deficits in immature neuronal morphology, intranuclear inclusions and decreased dentate gyrus volume were refractory to physical activity. Taken together our research indicates that exercise is not beneficial, and may be detrimental to a vulnerable nervous system. PMID:21152076

  13. Microribbon-based hydrogels accelerate stem cell-based bone regeneration in a mouse critical-size cranial defect model

    PubMed Central

    Han, Li-Hsin; Conrad, Bogdan; Chung, Michael T.; Deveza, Lorenzo; Jiang, Xinyi; Wang, Andrew; Butte, Manish J.; Longaker, Michael T.; Wan, Derrick; Yang, Fan

    2016-01-01

    Stem cell-based therapies hold great promise for enhancing tissue regeneration. However, the majority of cells die shortly after transplantation, which greatly diminishes the efficacy of stem cell-based therapies. Poor cell engraftment and survival remain a major bottleneck to fully exploiting the power of stem cells for regenerative medicine. Biomaterials such as hydrogels can serve as artificial matrices to protect cells during delivery and guide desirable cell fates. However, conventional hydrogels often lack macroporosity, which restricts cell proliferation and delays matrix deposition. Here we report the use of injectable, macroporous microribbon (µRB) hydrogels as stem cell carriers for bone repair, which supports direct cell encapsulation into a macroporous scaffold with rapid spreading. When transplanted in a criticalsized, mouse cranial defect model, µRB-based hydrogels significantly enhanced the survival of transplanted adipose-derived stromal cells (ADSCs) (81%) and enabled up to three-fold cell proliferation after 7 days. In contrast, conventional hydrogels only led to 27% cell survival, which continued to decrease over time. MicroCT imaging showed µRBs enhanced and accelerated mineralized bone repair compared to hydrogels (61% vs. 34% by week 6), and stem cells were required for bone repair to occur. These results suggest that paracrine signaling of transplanted stem cells are responsible for the observed bone repair, and enhancing cell survival and proliferation using µRBs further promoted the paracrine-signaling effects of ADSCs for stimulating endogenous bone repair. We envision µRB-based scaffolds can be broadly useful as a novel scaffold for enhancing stem cell survival and regeneration of other tissue types. PMID:26991141

  14. Mechanisms underlying insulin deficiency-induced acceleration of β-amyloidosis in a mouse model of Alzheimer's disease.

    PubMed

    Devi, Latha; Alldred, Melissa J; Ginsberg, Stephen D; Ohno, Masuo

    2012-01-01

    Although evidence is accumulating that diabetes mellitus is an important risk factor for sporadic Alzheimer's disease (AD), the mechanisms by which defects in insulin signaling may lead to the acceleration of AD progression remain unclear. In this study, we applied streptozotocin (STZ) to induce experimental diabetes in AD transgenic mice (5XFAD model) and investigated how insulin deficiency affects the β-amyloidogenic processing of amyloid precursor protein (APP). Two and half months after 5XFAD mice were treated with STZ (90 mg/kg, i.p., once daily for two consecutive days), they showed significant reductions in brain insulin levels without changes in insulin receptor expression. Concentrations of cerebral amyloid-β peptides (Aβ40 and Aβ42) were significantly increased in STZ-treated 5XFAD mice as compared with vehicle-treated 5XFAD controls. Importantly, STZ-induced insulin deficiency upregulated levels of both β-site APP cleaving enzyme 1 (BACE1) and full-length APP in 5XFAD mouse brains, which was accompanied by dramatic elevations in the β-cleaved C-terminal fragment (C99). Interestingly, BACE1 mRNA levels were not affected, whereas phosphorylation of the translation initiation factor eIF2α, a mechanism proposed to mediate the post-transcriptional upregulation of BACE1, was significantly elevated in STZ-treated 5XFAD mice. Meanwhile, levels of GGA3, an adapter protein responsible for sorting BACE1 to lysosomal degradation, are indistinguishable between STZ- and vehicle-treated 5XFAD mice. Moreover, STZ treatments did not affect levels of Aβ-degrading enzymes such as neprilysin and insulin-degrading enzyme (IDE) in 5XFAD brains. Taken together, our findings provide a mechanistic foundation for a link between diabetes and AD by demonstrating that insulin deficiency may change APP processing to favor β-amyloidogenesis via the translational upregulation of BACE1 in combination with elevations in its substrate, APP.

  15. The Role of a Prone Setup in Breast Radiation Therapy

    PubMed Central

    Huppert, Nelly; Jozsef, Gabor; DeWyngaert, Keith; Formenti, Silvia Chiara

    2011-01-01

    Most patients undergoing breast conservation therapy receive radiotherapy in the supine position. Historically, prone breast irradiation has been advocated for women with large pendulous breasts in order to decrease acute and late toxicities. With the advent of CT planning, the prone technique has become both feasible and reproducible. It was shown to be advantageous not only for women with larger breasts but in most patients since it consistently reduces, if not eliminates, the inclusion of heart and lung within the field. The prone setup has been accepted as the best localizing position for both MRI and stereotactic biopsy, but its adoption has been delayed in radiotherapy. New technological advances including image-modulated radiation therapy and image-guided radiation therapy have made possible the exploration of accelerated fractionation schemes with a concomitant boost to the tumor bed in the prone position, along with better imaging and verification of reproducibility of patient setup. This review describes some of the available techniques for prone breast radiotherapy and the available experience in their application. The NYU prone breast radiotherapy approach is discussed, including a summary of the results from several prospective trials. PMID:22655240

  16. The role of a prone setup in breast radiation therapy.

    PubMed

    Huppert, Nelly; Jozsef, Gabor; Dewyngaert, Keith; Formenti, Silvia Chiara

    2011-01-01

    Most patients undergoing breast conservation therapy receive radiotherapy in the supine position. Historically, prone breast irradiation has been advocated for women with large pendulous breasts in order to decrease acute and late toxicities. With the advent of CT planning, the prone technique has become both feasible and reproducible. It was shown to be advantageous not only for women with larger breasts but in most patients since it consistently reduces, if not eliminates, the inclusion of heart and lung within the field. The prone setup has been accepted as the best localizing position for both MRI and stereotactic biopsy, but its adoption has been delayed in radiotherapy. New technological advances including image-modulated radiation therapy and image-guided radiation therapy have made possible the exploration of accelerated fractionation schemes with a concomitant boost to the tumor bed in the prone position, along with better imaging and verification of reproducibility of patient setup. This review describes some of the available techniques for prone breast radiotherapy and the available experience in their application. The NYU prone breast radiotherapy approach is discussed, including a summary of the results from several prospective trials.

  17. Error-prone translesion replication of damaged DNA suppresses skin carcinogenesis by controlling inflammatory hyperplasia

    PubMed Central

    Tsaalbi-Shtylik, Anastasia; Verspuy, Johan W. A.; Jansen, Jacob G.; Rebel, Heggert; Carlée, Leone M.; van der Valk, Martin A.; Jonkers, Jos; de Gruijl, Frank R.; de Wind, Niels

    2009-01-01

    The induction of skin cancer involves both mutagenic and proliferative responses of the epidermis to ultraviolet (UV) light. It is believed that tumor initiation requires the mutagenic replication of damaged DNA by translesion synthesis (TLS) pathways. The mechanistic basis for the induction of proliferation, providing tumor promotion, is poorly understood. Here, we have investigated the role of TLS in the initiation and promotion of skin carcinogenesis, using a sensitive nucleotide excision repair-deficient mouse model that carries a hypomorphic allele of the error-prone TLS gene Rev1. Despite a defect in UV-induced mutagenesis, skin carcinogenesis was accelerated in these mice. This paradoxical phenotype was caused by the induction of inflammatory hyperplasia of the mutant skin that provides strong tumor promotion. The induction of hyperplasia was associated with mild and transient replicational stress of the UV-damaged genome, triggering DNA damage signaling and senescence. The concomitant expression of Interleukin-6 (IL-6) is in agreement with an executive role for IL-6 and possibly other cytokines in the autocrine induction of senescence and the paracrine induction of inflammatory hyperplasia. In conclusion, error-prone TLS suppresses tumor-promoting activities of UV light, thereby controlling skin carcinogenesis. PMID:20007784

  18. Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin.

    PubMed

    Miyazaki, M; Takemura, N; Watanabe, S; Hata, N; Misawa, Y; Okuyama, H

    2000-01-03

    We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.

  19. Relative Reduction of Endothelial Nitric-Oxide Synthase Expression and Transcription in Atherosclerosis-Prone Regions of the Mouse Aorta and in an in Vitro Model of Disturbed Flow

    PubMed Central

    Won, Doyon; Zhu, Su-Ning; Chen, Mian; Teichert, Anouk-Martine; Fish, Jason E.; Matouk, Charles C.; Bonert, Michael; Ojha, Matadial; Marsden, Philip A.; Cybulsky, Myron I.

    2007-01-01

    Atherosclerosis develops in distinct regions of the arterial tree. Defining patterns and mechanisms of endothelial cell gene expression in different regions of normal arteries is key to understanding the initial molecular events in atherogenesis. In this study, we demonstrated that the expression of endothelial nitric-oxide synthase (eNOS), an atheroprotective gene, and its phosphorylation on Ser1177, a marker of activity, were lower in regions of the normal mouse aorta that are predisposed to atherosclerosis. The same expression pattern was observed in mouse strains that are both susceptible and resistant to atherosclerosis, and the topography of eNOS expression was inverse to p65, the main nuclear factor-κB subunit. Modeling of disturbed and uniform laminar flow in vitro reproduced the expression patterns of eNOS and p65 that were found in vivo. Heterogeneous nuclear RNA expression and RNA polymerase II chromosome immunoprecipitation studies demonstrated that regulation of transcription contributed to increased eNOS expression in response to shear stress. In vivo, the transcription of eNOS was reduced in regions of the mouse aorta predisposed to atherosclerosis, as defined by reporter gene expression in eNOS promoter-β-galactosidase reporter transgenic mice. These data suggest that disturbed hemodynamic patterns found at arterial branches and curvatures uniquely modulate endothelial cell gene expression by regulating transcription, potentially explaining why these regions preferentially develop atherosclerosis when risk factors such as hypercholesterolemia are introduced. PMID:17982133

  20. Developing a framework for predicting upper extremity muscle activities, postures, velocities, and accelerations during computer use: the effect of keyboard use, mouse use, and individual factors on physical exposures.

    PubMed

    Bruno Garza, Jennifer L; Catalano, Paul J; Katz, Jeffrey N; Huysmans, Maaike A; Dennerlein, Jack T

    2012-01-01

    Prediction models were developed based on keyboard and mouse use in combination with individual factors that could be used to predict median upper extremity muscle activities, postures, velocities, and accelerations experienced during computer use. In the laboratory, 25 participants performed five simulated computer trials with different amounts of keyboard and mouse use ranging from a highly keyboard-intensive trial to a highly mouse-intensive trial. During each trial, muscle activity and postures of the shoulder and wrist and velocities and accelerations of the wrists, along with percentage keyboard and mouse use, were measured. Four individual factors (hand length, shoulder width, age, and gender) were also measured on the day of data collection. Percentage keyboard and mouse use explained a large amount of the variability in wrist velocities and accelerations. Although hand length, shoulder width, and age were each significant predictors of at least one median muscle activity, posture, velocity, or acceleration exposure, these individual factors explained very little variability in addition to percentage keyboard and mouse use in any of the physical exposures investigated. The amounts of variability explained for models predicting median wrist velocities and accelerations ranged from 75 to 84% but were much lower for median muscle activities and postures (0-50%). RMS errors ranged between 8 to 13% of the range observed. While the predictions for wrist velocities and accelerations may be able to be used to improve exposure assessment for future epidemiologic studies, more research is needed to identify other factors that may improve the predictions for muscle activities and postures.

  1. Accelerating discovery for complex neurological and behavioral disorders through systems genetics and integrative genomics in the laboratory mouse.

    PubMed

    Bubier, Jason A; Chesler, Elissa J

    2012-04-01

    Recent advances in systems genetics and integrative functional genomics have greatly improved the study of complex neurological and behavioral traits. The methods developed for the integrated characterization of new, high-resolution mouse genetic reference populations and systems genetics enable behavioral geneticists an unprecedented opportunity to address questions of the molecular basis of neurological and psychiatric disorders and their comorbidities. Integrative genomics augment these strategies by enabling rapid informatics-assisted candidate gene prioritization, cross-species translation, and mechanistic comparison across related disorders from a wealth of existing data in mouse and other model organisms. Ultimately, through these complementary approaches, finding the mechanisms and sources of genetic variation underlying complex neurobehavioral disease related traits is becoming tractable. Furthermore, these methods enable categorization of neurobehavioral disorders through their underlying biological basis. Together, these model organism-based approaches can lead to a refinement of diagnostic categories and targeted treatment of neurological and psychiatric disease.

  2. Vegetation fire proneness in Europe

    NASA Astrophysics Data System (ADS)

    Pereira, Mário; Aranha, José; Amraoui, Malik

    2015-04-01

    Fire selectivity has been studied for vegetation classes in terms of fire frequency and fire size in a few European regions. This analysis is often performed along with other landscape variables such as topography, distance to roads and towns. These studies aims to assess the landscape sensitivity to forest fires in peri-urban areas and land cover changes, to define landscape management guidelines and policies based on the relationships between landscape and fires in the Mediterranean region. Therefore, the objectives of this study includes the: (i) analysis of the spatial and temporal variability statistics within Europe; and, (ii) the identification and characterization of the vegetated land cover classes affected by fires; and, (iii) to propose a fire proneness index. The datasets used in the present study comprises: Corine Land Cover (CLC) maps for 2000 and 2006 (CLC2000, CLC2006) and burned area (BA) perimeters, from 2000 to 2013 in Europe, provided by the European Forest Fire Information System (EFFIS). The CLC is a part of the European Commission programme to COoRdinate INformation on the Environment (Corine) and it provides consistent, reliable and comparable information on land cover across Europe. Both the CLC and EFFIS datasets were combined using geostatistics and Geographical Information System (GIS) techniques to access the spatial and temporal evolution of the types of shrubs and forest affected by fires. Obtained results confirms the usefulness and efficiency of the land cover classification scheme and fire proneness index which allows to quantify and to compare the propensity of vegetation classes and countries to fire. As expected, differences between northern and southern Europe are notorious in what concern to land cover distribution, fire incidence and fire proneness of vegetation cover classes. This work was supported by national funds by FCT - Portuguese Foundation for Science and Technology, under the project PEst-OE/AGR/UI4033/2014 and by

  3. Defective ATM-Kap-1-mediated chromatin remodeling impairs DNA repair and accelerates senescence in progeria mouse model.

    PubMed

    Liu, Baohua; Wang, Zimei; Ghosh, Shrestha; Zhou, Zhongjun

    2013-04-01

    ATM-mediated phosphorylation of KAP-1 triggers chromatin remodeling and facilitates the loading and retention of repair proteins at DNA lesions. Mouse embryonic fibroblasts (MEFs) derived from Zmpste24(-/-) mice undergo early senescence, attributable to delayed recruitment of DNA repair proteins. Here, we show that ATM-Kap-1 signaling is compromised in Zmpste24(-/-) MEFs, leading to defective DNA damage-induced chromatin remodeling. Knocking down Kap-1 rescues impaired chromatin remodeling, defective DNA repair and early senescence in Zmpste24(-/-) MEFs. Thus, ATM-Kap-1-mediated chromatin remodeling plays a critical role in premature aging, carrying significant implications for progeria therapy.

  4. Prone and supine percutaneous nephrolithotomy.

    PubMed

    Lucarelli, G; Breda, A

    2013-06-01

    Since the first successful stone extraction through a nephrostomy in 1976, percutaneous nephrolithotomy (PCNL) has became the preferred procedure especially for treatment of large, complex and staghorn calculi. For decades this method has been performed with the patient in the prone position. More recently, particular interest has been taken on supine PCNL due to less anestesiological risks and the possibility of simultaneous anterograde and retrograde access to the whole urinary tract. Although many retrospective studies have been published, only two prospective trials comparing the two positions are reported in the literature. The best access to PCNL represents still a controversial issue. The overall experience reported in literature indicates that each modality is equally feasible and safe. Therefore, to date the surgeon's preference is the prime indication to one access over the other.

  5. Changes in expressions of proinflammatory cytokines IL-1beta, TNF-alpha and IL-6 in the brain of senescence accelerated mouse (SAM) P8.

    PubMed

    Tha, K K; Okuma, Y; Miyazaki, H; Murayama, T; Uehara, T; Hatakeyama, R; Hayashi, Y; Nomura, Y

    2000-12-01

    The senescence-accelerated mouse (SAM) is known to be a murine model for accelerated aging. The SAMP8 strain shows age-related deterioration of learning and memory at an earlier age than control mice (SAMR1). In the present study, we investigated the changes in expressions of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the brain of SAMP8. In the hippocampus of 10 months old SAMP8, the expression of IL-1 mRNA was significantly elevated in comparison with that of SAMR1. In both strains of SAMs, increases in IL-1beta protein in the brain were observed at 10 months of age compared with 2 and 5 months. The only differences found between the strain in protein levels were at 10 months and were elevations in IL-1beta in the hippocampus and hypothalamus, and in TNF-alpha and IL-6 in the cerebral cortex and the hippocampus in SAMP8 as compared with SAMR1. However, lipopolysaccharide-induced increases in the expression of these cytokines in brain did not differ between SAMP8 and SAMR1. Increases in expression of proinflammatory cytokines in the brain may be involved in the age-related neural dysfunction and/or learning deficiency in SAMP8.

  6. Stat3 accelerates Myc induced tumor formation while reducing growth rate in a mouse model of breast cancer

    PubMed Central

    Jhan, Jing-Ru; Andrechek, Eran R.

    2016-01-01

    Elevated Myc expression has been noted in basal breast cancer but therapies targeting Myc directly are lacking. It is therefore critical to characterize the interaction of Myc with other genes and pathways to uncover future potential therapeutic strategies. In this study, we bioinformatically predicted a role for Stat3 in Myc induced mammary tumors and tested it using mouse models. During normal mammary function, loss of Stat3 in Myc transgenic dams resulted in lethality of pups due to lactation deficiencies. We also observed that deletion of Stat3 in the mammary glands of MMTV-Myc mice unexpectedly resulted in increased and earlier hyperplasia and expedited tumorigenesis. However, despite arising earlier, Myc tumors lacking Stat3 grew more slowly with alterations in the resulting histological subtypes, including a dramatic increase in EMT-like tumors. We also observed that these tumors had impaired angiogenesis and a slight decrease in lung metastases. This metastatic finding is distinct from previously published findings in both MMTV-Neu and MMTV-PyMT mouse models. Together, the literature and our current research demonstrate that Stat3 can function as an oncogene or as a tumor repressor depending on the oncogenic driver and developmental context. PMID:27589562

  7. Prone positioning in acute respiratory distress syndrome.

    PubMed

    Gibson, Kristy; Dufault, Marlene; Bergeron, Kathy

    2015-08-12

    Acute respiratory distress syndrome (ARDS) is a condition with a high morbidity and mortality rate, and treatment is often long and costly. Prone positioning is a rarely used intervention for patients with this syndrome, although research suggests it may be effective. A literature search was undertaken to examine the effects of prone positioning on oxygenation, morbidity and mortality in patients with ARDS. It revealed that prone positioning, when used with low tidal volume ventilation over an extended period, may reduce mortality rates in selected patients with severe ARDS. The selection of patients with severe ARDS for prone positioning should be done on a case-by-case basis to maximise benefits and minimise complications. Further research is required on the use of prone positioning in patients with severe ARDS to support or disclaim the therapy's use in practice, and to compare confounding variables such as ideal prone duration and mechanical versus manual pronation.

  8. HMJ-53A accelerates slow inactivation gating of voltage-gated K+ channels in mouse neuroblastoma N2A cells.

    PubMed

    Chao, Chia-Chia; Shieh, Jeffrey; Kuo, Sheng-Chu; Wu, Bor-Tsang; Hour, Mann-Jen; Leung, Yuk-Man

    2008-06-01

    Voltage-gated K(+) (Kv) channels are important in repolarization of excitable cells such as neurons and endocrine cells. Kv channel gating exhibits slow inactivation (slow current decay) during continuous depolarization. The molecular mechanism involved in such slow inactivation is not completely understood, but evidence has suggested that it involves a restriction of the outer channel pore surrounding the selectivity filter. Pharmacological tools probing this slow inactivation process are scarce. In this work we reported that bath application of HMJ-53A (30 microM), a novel compound, could drastically speed up the slow decay (decay tau=1677+/-120 ms and 85.6+/-7.7 ms, respectively, in the absence and presence of HMJ-53A) of Kv currents in neuroblastoma N2A cells. HMJ-53A also significantly left-shifted the steady-state inactivation curve by 12 mV. HMJ-53A, however, did not affect voltage-dependence of activation and the kinetics of channel activation. Intracellular application of this drug through patch pipette dialysis was ineffective at all in accelerating the slow current decay, suggesting that HMJ-53A acted extracellularly. Blockade of currents by HMJ-53A did not require an open state of channels. In addition, the inactivation time constants and percentage block of Kv currents in the presence of HMJ-53A were independent of the (i) degree of depolarization and (ii) intracellular K(+) concentration. Therefore, this drug did not appear to directly occlude the outer channel pore during stimulation (depolarization). Taken together, our results suggest that HMJ-53A selectively affected (accelerated) the slow inactivation gating process of Kv channels, and could thus be a selective and novel probe for the inactivation gate.

  9. Mono(2-Ethylhexyl) Phthalate Accelerates Early Folliculogenesis and Inhibits Steroidogenesis in Cultured Mouse Whole Ovaries and Antral Follicles1

    PubMed Central

    Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Flaws, Jodi A.

    2015-01-01

    Humans are ubiquitously exposed to di(2-ethylhexyl) phthalate (DEHP), which is an environmental toxicant present in common consumer products. DEHP potentially targets the ovary through its metabolite mono(2-ethylhexyl) phthalate (MEHP). However, the direct effects of MEHP on ovarian folliculogenesis and steroidogenesis, two processes essential for reproductive and nonreproductive health, are unknown. The present study tested the hypotheses that MEHP directly accelerates early folliculogenesis via overactivation of phosphatidylinositol 3-kinase (PI3K) signaling, a pathway that regulates primordial follicle quiescence and activation, and inhibits the synthesis of steroid hormones by decreasing steroidogenic enzyme levels. Neonatal ovaries from CD-1 mice were cultured for 6 days with vehicle control, DEHP, or MEHP (0.2–20 μg/ml) to assess the direct effects on folliculogenesis and PI3K signaling. Further, antral follicles from adult CD-1 mice were cultured with vehicle control or MEHP (0.1–10 μg/ml) for 24–96 h to establish the temporal effects of MEHP on steroid hormones and steroidogenic enzymes. In the neonatal ovaries, MEHP, but not DEHP, decreased phosphatase and tensin homolog levels and increased phosphorylated protein kinase B levels, leading to a decrease in the percentage of germ cells and an increase in the percentage of primary follicles. In the antral follicles, MEHP decreased the mRNA levels of 17alpha-hydroxylase-17,20-desmolase, 17beta-hydroxysteroid dehydrogenase, and aromatase leading to a decrease in testosterone, estrone, and estradiol levels. Collectively, MEHP mediates the effect of DEHP on accelerated folliculogenesis via overactivating PI3K signaling and inhibits steroidogenesis by decreasing steroidogenic enzyme levels. PMID:25810477

  10. Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium.

    PubMed

    Pacheco-Pinedo, Eugenia C; Durham, Amy C; Stewart, Kathleen M; Goss, Ashley M; Lu, Min Min; Demayo, Francesco J; Morrisey, Edward E

    2011-05-01

    Although mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcome among patients with lung cancer bearing similar mutations, suggesting that other pathways are important. Wnt/β-catenin signaling is a known oncogenic pathway that plays a well-defined role in colon and skin cancer; however, its role in lung cancer is unclear. We have shown here that activation of Wnt/β-catenin in the bronchiolar epithelium of the adult mouse lung does not itself promote tumor development. However, concurrent activation of Wnt/β-catenin signaling and expression of a constitutively active Kras mutant (KrasG12D) led to a dramatic increase in both overall tumor number and size compared with KrasG12D alone. Activation of Wnt/β-catenin signaling altered the KrasG12D tumor phenotype, resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This was associated with decreased E-cadherin expression at the cell surface, which may underlie the increased metastasis of tumors with active Wnt/β-catenin signaling. Together, these data suggest that activation of Wnt/β-catenin signaling can combine with other oncogenic pathways in lung epithelium to produce a more aggressive tumor phenotype by imposing an embryonic distal progenitor phenotype and by decreasing E-cadherin expression.

  11. Obox4-silencing-activated STAT3 and MPF/MAPK signaling accelerate nuclear membrane breakdown in mouse oocytes.

    PubMed

    Lee, Hyun-Seo; Kim, Kyeoung-Hwa; Kim, Eun-Young; Lee, Su-Yeon; Ko, Jung-Jae; Lee, Kyung-Ah

    2016-04-01

    Mouse oocytes begin to mature in vitro once liberated from ovarian follicles. Previously, we showed that oocyte-specific homeobox 4 (Obox4) is critical for maintaining the intact nuclear membrane of the germinal vesicle (GV) in oocytes and for completing meiosis at the metaphase I-II (MI-MII) transition. This study further examines the molecular mechanisms of OBOX4 in regulating GV nuclear membrane breakdown. Maturation-promoting factor (MPF) and MAPK are normally inactive in GV stage oocytes but were activated prematurely in arrested GV stage oocytes by 3-isobutyl-1-metyl-xanthine (IBMX) in vitro after Obox4 RNA interference (RNAi). Furthermore, signal transducer and activator of transcription 3 (STAT3) was significantly activated by Obox4 RNAi. We confirmed that this Obox4 RNAi-induced premature STAT3 and MPF/MAPK activation at the GV stage provoked subsequent GV breakdown (GVBD) despite the opposing force of high cAMP in the IBMX-supplemented medium to maintain intact GV. When cumulus-oocyte complexes were exposed to interferon α (IFNA), a STAT3 activator, oocytes matured and cumulus cells expanded to resume nuclear maturation in IBMX-supplemented medium, suggesting that STAT3 activation is sufficient for stimulating the continuation of meiosis. Using Stattic, a specific STAT3 inhibitor, we confirmed that GVBD involves STAT3 activation in Obox4-silenced oocytes. Based on these findings, we concluded that i) Obox4 is an important upstream regulator of MPF/MAPK and STAT3 signaling, and ii) Obox4 is a key regulator of the GV arrest mechanism in oocytes.

  12. Accelerated activation of SOCE current in myotubes from two mouse models of anesthetic- and heat-induced sudden death.

    PubMed

    Yarotskyy, Viktor; Protasi, Feliciano; Dirksen, Robert T

    2013-01-01

    Store-operated calcium entry (SOCE) channels play an important role in Ca(2+) signaling. Recently, excessive SOCE was proposed to play a central role in the pathogenesis of malignant hyperthermia (MH), a pharmacogenic disorder of skeletal muscle. We tested this hypothesis by characterizing SOCE current (ISkCRAC) magnitude, voltage dependence, and rate of activation in myotubes derived from two mouse models of anesthetic- and heat-induced sudden death: 1) type 1 ryanodine receptor (RyR1) knock-in mice (Y524S/+) and 2) calsequestrin 1 and 2 double knock-out (dCasq-null) mice. ISkCRAC voltage dependence and magnitude at -80 mV were not significantly different in myotubes derived from wild type (WT), Y524S/+ and dCasq-null mice. However, the rate of ISkCRAC activation upon repetitive depolarization was significantly faster at room temperature in myotubes from Y524S/+ and dCasq-null mice. In addition, the maximum rate of ISkCRAC activation in dCasq-null myotubes was also faster than WT at more physiological temperatures (35-37°C). Azumolene (50 µM), a more water-soluble analog of dantrolene that is used to reverse MH crises, failed to alter ISkCRAC density or rate of activation. Together, these results indicate that while an increased rate of ISkCRAC activation is a common characteristic of myotubes derived from Y524S/+ and dCasq-null mice and that the protective effects of azumolene are not due to a direct inhibition of SOCE channels.

  13. Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

    SciTech Connect

    Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko; Kikuta, Ayako; Nishiyama, Toshio

    2013-12-06

    Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.

  14. Mutation at the Polymerase Active Site of Mouse DNA Polymerase δ Increases Genomic Instability and Accelerates Tumorigenesis▿

    PubMed Central

    Venkatesan, Ranga N.; Treuting, Piper M.; Fuller, Evan D.; Goldsby, Robert E.; Norwood, Thomas H.; Gooley, Ted A.; Ladiges, Warren C.; Preston, Bradley D.; Loeb, Lawrence A.

    2007-01-01

    Mammalian DNA polymerase δ (Pol δ) is believed to replicate a large portion of the genome and to synthesize DNA in DNA repair and genetic recombination pathways. The effects of mutation in the polymerase domain of this essential enzyme are unknown. Here, we generated mice harboring an L604G or L604K substitution in highly conserved motif A in the polymerase active site of Pol δ. Homozygous Pold1L604G/L604G and Pold1L604K/L604K mice died in utero. However, heterozygous animals were viable and displayed no overall increase in disease incidence, indicative of efficient compensation for the defective mutant polymerase. The life spans of wild-type and heterozygous Pold1+/L604G mice did not differ, while that of Pold1+/L604K mice was reduced by 18%. Cultured embryonic fibroblasts from the heterozygous strains exhibited comparable increases in both spontaneous mutation rate and chromosome aberrations. We observed no significant increase in cancer incidence; however, Pold1+/L604K mice bearing histologically diagnosed tumors died at a younger median age than wild-type mice. Our results indicate that heterozygous mutation at L604 in the polymerase active site of DNA polymerase δ reduces life span, increases genomic instability, and accelerates tumorigenesis in an allele-specific manner, novel findings that have implications for human cancer. PMID:17785453

  15. The anti-aging effects of LW-AFC via correcting immune dysfunctions in senescence accelerated mouse resistant 1 (SAMR1) strain

    PubMed Central

    Wang, Jianhui; Cheng, Xiaorui; Zhang, Xiaorui; Cheng, Junping; Xu, Yiran; Zeng, Ju; Zhou, Wenxia; Zhang, Yongxiang

    2016-01-01

    Although there were considerable advances in the anti-aging medical field, it is short of therapeutic drug for anti-aging. Mounting evidence indicates that the immunosenescence is the key physiopathological mechanism of aging. This study showed the treatment of LW-AFC, an herbal medicine, decreased the grading score of senescence, increased weight, prolonged average life span and ameliorated spatial memory impairment in 12- and 24-month-old senescence accelerated mouse resistant 1 (SAMR1) strain. And these anti-aging effects of LW-AFC were more excellent than melatonin. The administration of LW-AFC enhanced ConA- and LPS-induced splenocyte proliferation in aged SAMR1 mice. The treatment of LW-AFC not only reversed the decreased the proportions of helper T cells, suppressor T cells and B cells, the increased regulatory T cells in the peripheral blood of old SAMR1 mice, but also could modulate the abnormal secretion of IL-1β, IL-2, IL-6, IL-17, IL-23, GM-CSF, IFN-γ, TNF-α, TNF-β, RANTES, eotaxin, MCP-1, IL-4, IL-5, IL-10 and G-CSF. These data indicated that LW-AFC reversed the immunosenescence status by restoring immunodeficiency and decreasing chronic inflammation and suggested LW-AFC may be an effective anti-aging agent. PMID:27105505

  16. [Ameliorating effects of dan-shen and its major ingredient calcium/magnesium lithospermate B on cognitive deficiencies in senescence-accelerated mouse].

    PubMed

    Nomura, Y; Arima, T; Namba, T; Hattori, M; Kadota, S

    1997-10-01

    Effect of the long-term treatment with a Dan-Shen (Salviae miltiorrhizae radix) methanol extract (DME) or its major ingredient lithospermate B (LSB) on memory and learning in scenescence-accelerated mouse (SAM) was investigated by means of Morris's water maze task. DME or LSB treatment significantly decreased the escape latency in the P8 strain of SAM (SAMP8), which strain spontaneously develops learning deficits. These results suggest that DME and LSB treatment improved spacial learning. Neurochemical investigations indicated that both drugs did not affect the cholinergic system, but enhanced functions of the glutamate-PKC system in hippocampus, since the increases in [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]-cyclohepten-5,10-imine maleate) binding in cortex and [3H]PDBu (phorbol 12,13-dibutyrate) binding in hippocampus were observed in DME and LSB treatments. Our previous studies indicate the decrease in PDBu binding and NMDA receptor-mediated functions in SAMP8 brain. Thus, it is suggested that 1) Methanol extract of Dan-Shen is effective for prevention of spacial learning deficit caused with aging, 2) lithospermate B is one of the active ingredients, 3) SAMP8 is useful model animal to investigate drugs for anti-aging or anti-dementia.

  17. The anti-aging effects of LW-AFC via correcting immune dysfunctions in senescence accelerated mouse resistant 1 (SAMR1) strain.

    PubMed

    Wang, Jianhui; Cheng, Xiaorui; Zhang, Xiaorui; Cheng, Junping; Xu, Yiran; Zeng, Ju; Zhou, Wenxia; Zhang, Yongxiang

    2016-05-10

    Although there were considerable advances in the anti-aging medical field, it is short of therapeutic drug for anti-aging. Mounting evidence indicates that the immunosenescence is the key physiopathological mechanism of aging. This study showed the treatment of LW-AFC, an herbal medicine, decreased the grading score of senescence, increased weight, prolonged average life span and ameliorated spatial memory impairment in 12- and 24-month-old senescence accelerated mouse resistant 1 (SAMR1) strain. And these anti-aging effects of LW-AFC were more excellent than melatonin. The administration of LW-AFC enhanced ConA- and LPS-induced splenocyte proliferation in aged SAMR1 mice. The treatment of LW-AFC not only reversed the decreased the proportions of helper T cells, suppressor T cells and B cells, the increased regulatory T cells in the peripheral blood of old SAMR1 mice, but also could modulate the abnormal secretion of IL-1β, IL-2, IL-6, IL-17, IL-23, GM-CSF, IFN-γ, TNF-α, TNF-β, RANTES, eotaxin, MCP-1, IL-4, IL-5, IL-10 and G-CSF. These data indicated that LW-AFC reversed the immunosenescence status by restoring immunodeficiency and decreasing chronic inflammation and suggested LW-AFC may be an effective anti-aging agent.

  18. The Concept of Accident Proneness: A Review

    PubMed Central

    Froggatt, Peter; Smiley, James A.

    1964-01-01

    The term accident proneness was coined by psychological research workers in 1926. Since then its concept—that certain individuals are always more likely than others to sustain accidents, even though exposed to equal risk—has been questioned but seldom seriously challenged. This article describes much of the work and theory on which this concept is based, details the difficulties encountered in obtaining valid information and the interpretative errors that can arise from the examination of imperfect data, and explains why accident proneness became so readily accepted as an explanation of the facts. A recent hypothesis of accident causation, namely that a person's accident liability may vary from time to time, is outlined, and the respective abilities of this and of accident proneness to accord with data from the more reliable literature are examined. The authors conclude that the hypothesis of individual variation in liability is more realistic and in better agreement with the data than is accident proneness. PMID:14106130

  19. Men More Prone to Severe Psoriasis

    MedlinePlus

    ... fullstory_164498.html Men More Prone to Severe Psoriasis: Study Researchers say this may explain why more ... 2017 THURSDAY, April 6, 2017 (HealthDay News) -- Severe psoriasis is much more common in men than women, ...

  20. Smokers Prone to Problems After Joint Replacement

    MedlinePlus

    ... fullstory_164137.html Smokers Prone to Problems After Joint Replacement: Study Cessation programs help reduce the rate ... that smokers do worse than non-smokers after joint replacements, and now this research shows there's good ...

  1. Effect of Low-Magnitude, High-Frequency Vibration Treatment on Retardation of Sarcopenia: Senescence-Accelerated Mouse-P8 Model.

    PubMed

    Guo, An-Yun; Leung, Kwok-Sui; Qin, Jiang-Hui; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

    2016-08-01

    Sarcopenia-related falls and fall-related injuries in community-dwelling elderly people garnered more and more interest in recent years. Low-magnitude high-frequency vibration (LMHFV) was proven beneficial to musculoskeletal system and recommended for sarcopenia treatment. This study aimed to evaluate the effects of LMHFV on the sarcopenic animals and explore the mechanism of the stimulatory effects. Senescence-accelerated mouse P8 (SAMP8) mice at month 6 were randomized into control (Ctrl) and vibration (Vib) groups and the mice in the Vib group were given LMHFV (0.3 g, 20 min/day, 5 days/week) treatment. At months 0, 1, 2, 3, and 4 post-treatment, muscle mass, structure, and function were assessed. The potential proliferation capacity of the muscle was also evaluated by investigating satellite cells (SCs) pool and serum myostatin expression. At late stage, the mice in the Vib group showed higher muscle strength (month 4, p = 0.028). Generally, contractibility was significantly improved by LMHFV (contraction time [CT], p = 0.000; half-relaxation time [RT50], p = 0.000). Enlarged cross-sectional area of fiber type IIA was observed in the Vib group when compared with Ctrl group (p = 0.000). No significant difference of muscle mass was observed. The promotive effect of LMHFV on myoregeneration was reflected by suppressed SC pool reduction (month 3, p = 0.000; month 4, p = 0.000) and low myostatin expression (p = 0.052). LMHFV significantly improved the structural and functional outcomes of the skeletal muscle, hence retarding the progress of sarcopenia in SAMP8. It would be a good recommendation for prevention of the diseases related to skeletal muscle atrophy.

  2. ApoE4 expression accelerates hippocampus-dependent cognitive deficits by enhancing Aβ impairment of insulin signaling in an Alzheimer’s disease mouse model

    PubMed Central

    Chan, Elizabeth S.; Shetty, Mahesh Shivarama; Sajikumar, Sreedharan; Chen, Christopher; Soong, Tuck Wah; Wong, Boon-Seng

    2016-01-01

    The apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for Alzheimer’s disease (AD). The AD brain was shown to be insulin resistant at end stage, but the interplay between insulin signaling, ApoE4 and Aβ across time, and their involvement in memory decline is unclear. To investigate insulin response in the ageing mouse hippocampus, we crossed the human ApoE-targeted replacement mice with the mutant human amyloid precursor protein (APP) mice (ApoExAPP). While hippocampal Aβ levels were comparable between ApoE3xAPP and ApoE4xAPP mice at 26 weeks, insulin response was impaired in the ApoE4xAPP hippocampus. Insulin treatment was only able to stimulate insulin signaling and increased AMPA-GluR1 phosphorylation in forskolin pre-treated hippocampal slices from ApoE3xAPP mice. In ApoE4xAPP mice, insulin dysfunction was also associated with poorer spatial memory performance. Using dissociated hippocampal neuron in vitro, we showed that insulin response in ApoE3 and ApoE4 neurons increased AMPA receptor-mediated miniature excitatory postsynaptic current (mEPSC) amplitudes and GluR1-subunit insertion. Pre-treatment of ApoE3 neurons with Aβ42 did not affect insulin-mediated GluR1 subunit insertion. However, impaired insulin sensitivity observed only in the presence of ApoE4 and Aβ42, attenuated GluR1-subunit insertion. Taken together, our results suggest that ApoE4 enhances Aβ inhibition of insulin-stimulated AMPA receptor function, which accelerates memory impairment in ApoE4xAPP mice. PMID:27189808

  3. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    SciTech Connect

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D.; Formenti, Silvia C.

    2014-07-15

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm{sup 3}, mean 19.65 cm{sup 3}. In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm{sup 3}, mean 1.59 cm{sup 3}. There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and

  4. Ethnic and gender differences in boredom proneness

    SciTech Connect

    Gibson, G.S.; Morales,

    1996-02-01

    Although boredom may exhibit many shared elements, culturally specific attitudes have also been found to exist. The present paper investigated boredom proneness among African-American college students. Data from 120 participants on the Boredom Proneness (BP) Scale was analyzed and compared to cross-cultural participants. African-American females scored significantly higher than African-American males. Scores were presented from two other studies to show a comparative look at boredom proneness in five other ethnic groups. African-American females are the only female ethnic group to score higher on the BP Scale than their male counterparts. Additionally, overall African-Americans, were found to have higher BP scores than their Western counterparts.

  5. Isometric elbow extensors strength in supine- and prone-lying positions.

    PubMed

    Abdelzaher, Ibrahim E; Ababneh, Anas F; Alzyoud, Jehad M

    2013-01-01

    The purpose of this study was to compare isometric strength of elbow extensors measured in supine- and prone-lying positions at elbow flexion angles of 45 and 90 degrees. Twenty-two male subjects under single-blind procedures participated in the study. Each subject participated in both supine-lying and prone-lying measuring protocols. Calibrated cable tensiometer was used to measure isometric strength of the right elbow extensors and a biofeedback electromyography was used to assure no substitution movements from shoulder girdle muscles. The mean values of isometric strength of elbow extensors measured from supine-lying position at elbow flexion angles of 45 and 90 degrees were 11.1  ±  4.2 kg and 13.1  ±  4.6 kg, while those measured from prone-lying position were 9.9  ±  3.6 kg and 12  ±  4.2 kg, respectively. There is statistical significant difference between the isometric strength of elbow extensors measured from supine-lying position at elbow flexion angles of 45 and 90 degrees compared to that measured from prone-lying position (p  <  0.05). The results suggest that in manual muscle testing starting position can affect the isometric strength of elbow extensors since supine-lying starting position is better than prone-lying starting position.

  6. Senescence-accelerated Mice (SAMs) as a Model for Brain Aging and Immunosenescence

    PubMed Central

    Shimada, Atsuyoshi; Hasegawa-Ishii, Sanae

    2011-01-01

    The Senescence-Accelerated Mouse (SAM) represents a group of inbred mouse strains developed as a model for the study of human aging and age-related diseases. Senescence-prone (SAMP) strains exhibit an early onset of age-related decline in the peripheral immunity such as thymic involution, loss of CD4+ T cells, impaired helper T cell function, decreased antibody-forming capacity, dysfunction of antigen-presenting cells, decreased natural killer activity, increased auto-antibodies, and susceptibility to virus infection. Senescence-prone SAMP10 mice undergo age-related changes in the brain such as brain atrophy, shrinkage and loss of cortical neurons, retraction of cortical neuronal dendrites, loss of dendritic spines, loss of synapses, impaired learning and memory, depressive behavior, accumulation of neuronal DNA damage, neuronal ubiquitinated inclusions, reduced hippocampal cholinergic receptors, decreased neurotrophic factors, decreased hippocampal zinc and zinc transporters, increased sphyngomyelinase, and elevated oxidative-nitrative stress. Recent data indicating increased pro-inflammatory cytokines in the brain of SAMP10 mice are directing investigators toward an integration of immune and neural abnormalities to enhance understanding of the principles of brain aging. We highlight how mouse brain cells adopt cytokine-mediated responses and how SAMP10 mice are defective in these responses. SAMP10 model would be useful to study how age-related disturbances in peripheral immunity have an impact on dysregulation of brain tissue homeostasis, resulting in age-related neurodegeneration. PMID:22396891

  7. Reasoning, delusion proneness and stress: an experimental investigation.

    PubMed

    Keefe, Kristy M; Warman, Debbie M

    2011-01-01

    Previous studies have been inconsistent in demonstrating a relationship between delusion proneness and induced stress on reasoning biases. The present study was an experimental investigation of the role of stress in the form of feeling rushed, which has previously been shown to be related to the jumping-to-conclusions reasoning bias for delusion-prone individuals, on the reasoning of delusion-prone individuals. University students (n = 133) completed a measure of delusion proneness and were randomly assigned to either receive or not receive a stress induction in the form of a speeded subtraction task. All participants engaged in four trials of a probabilistic reasoning task. Delusion-prone and not delusion-prone participants performed similarly when there was no stress induction, but delusion-prone individuals demonstrated reasoning biases relative to not delusion-prone individuals when stress was induced. The reasoning of delusion-prone individuals may be particularly vulnerable when they feel rushed and in stressful conditions.

  8. Covariation bias in panic-prone individuals.

    PubMed

    Pauli, P; Montoya, P; Martz, G E

    1996-11-01

    Covariation estimates between fear-relevant (FR; emergency situations) or fear-irrelevant (FI; mushrooms and nudes) stimuli and an aversive outcome (electrical shock) were examined in 10 high-fear (panic-prone) and 10 low-fear respondents. When the relation between slide category and outcome was random (illusory correlation), only high-fear participants markedly overestimated the contingency between FR slides and shocks. However, when there was a high contingency of shocks following FR stimuli (83%) and a low contingency of shocks following FI stimuli (17%), the group difference vanished. Reversal of contingencies back to random induced a covariation bias for FR slides in high- and low-fear respondents. Results indicate that panic-prone respondents show a covariation bias for FR stimuli and that the experience of a high contingency between FR slides and aversive outcomes may foster such a covariation bias even in low-fear respondents.

  9. Paranormal belief and proneness to dissociation.

    PubMed

    Irwin, H J

    1994-12-01

    The study investigated the relationship between scores on paranormal belief and proneness to dissociation in a sample of 100 Australian students of psychology. Scores on dissociation were positively correlated with those on global paranormal belief and with belief in psi, precognition, spiritualism, and extraordinary life-forms. It is suggested that in some instances paranormal beliefs may be a component of a complex defensive framework constructed in the face of the perceived uncontrollability of life.

  10. Genetic Screen for PTSD-Prone Soldiers

    DTIC Science & Technology

    2009-08-01

    for determining genotypes at 8 loci in the calcyon gene which is strongly associated with attention deficit hyperactivity disorder (ADHD) and...associated with attention deficit hyperactivity disorder (ADHD) could be useful as an unbiased screen for PTSD-prone soldiers. Subjects participating... deficit / hyperactivity disorder . Mol. Psychiatry 10, 1117-1125. Li,J.Z., Absher,D.M., Tang,H., Southwick,A.M., Casto,A.M., Ramachandran,S., Cann,H.M

  11. Pathogenesis of A−β+ Ketosis-Prone Diabetes

    PubMed Central

    Patel, Sanjeet G.; Hsu, Jean W.; Jahoor, Farook; Coraza, Ivonne; Bain, James R.; Stevens, Robert D.; Iyer, Dinakar; Nalini, Ramaswami; Ozer, Kerem; Hampe, Christiane S.; Newgard, Christopher B.; Balasubramanyam, Ashok

    2013-01-01

    A−β+ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible β-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnitines, and amino acids were quantified in 20 KPD patients compared with 19 nondiabetic control subjects. Unique signatures in KPD—higher glutamate but lower glutamine and citrulline concentrations, increased β-hydroxybutyryl-carnitine, decreased isovaleryl-carnitine (a leucine catabolite), and decreased tricarboxylic acid (TCA) cycle intermediates—generated hypotheses that were tested through stable isotope/mass spectrometry protocols in nine new-onset, stable KPD patients compared with seven nondiabetic control subjects. Free fatty acid flux and acetyl CoA flux and oxidation were similar, but KPD had slower acetyl CoA conversion to β-hydroxybutyrate; higher fasting β-hydroxybutyrate concentration; slower β-hydroxybutyrate oxidation; faster leucine oxidative decarboxylation; accelerated glutamine conversion to glutamate without increase in glutamate carbon oxidation; and slower citrulline flux, with diminished glutamine amide–nitrogen transfer to citrulline. The confluence of metabolomic and kinetic data indicate a distinctive pathogenic sequence: impaired ketone oxidation and fatty acid utilization for energy, leading to accelerated leucine catabolism and transamination of α-ketoglutarate to glutamate, with impaired TCA anaplerosis of glutamate carbon. They highlight a novel process of defective energy production and ketosis in A−β+ KPD. PMID:23160531

  12. Assessment of trichloroethylene (TCE) exposure in murine strains genetically-prone and non-prone to develop autoimmune disease.

    PubMed

    Keil, Deborah E; Peden-Adams, Margie M; Wallace, Stacy; Ruiz, Phillip; Gilkeson, Gary S

    2009-04-01

    There is increasing laboratory and epidemiologic evidence relating exposure to trichloroethylene (TCE) with autoimmune disease including scleroderma and lupus. New Zealand Black/New Zealand White (NZBWF1) and B6C3F1 mice were exposed to TCE (0, 1, 400 or 14,000 ppb) via drinking water for 27 or 30 weeks, respectively. NZBWF1 mice spontaneously develop autoimmune disease while B6C3F1 mice, a standard strain used in immunotoxicology testing, are not genetically prone to develop autoimmune disease. During the TCE exposure period, serum levels of total IgG, and autoantibodies (anti-ssDNA, -dsDNA, and -glomerular antigen [GA]) were monitored. At the termination of the study, renal pathology, natural killer (NK) cell activity, total IgG levels, autoantibody production, T-cell activation, and lymphocytic proliferative responses were evaluated. TCE did not alter NK cell activity, or T- and B-cell proliferation in either strain. Numbers of activated T-cells (CD4+/CD44+) were increased in the B6C3F1 mice but not in the NZBWF1 mice. Renal pathology, as indicated by renal score, was significantly increased in the B6C3F1, but not in the NZBWF1 mice. Serum levels of autoantibodies to dsDNA and ssDNA were increased at more time points in B6C3F1, as compared to the NZBWF1 mice. Anti-GA autoantibodies were increased by TCE treatment in early stages of the study in NZBWF1 mice, but by 23 weeks of age, control levels were comparable to those of TCE-exposed animals. Serum levels anti-GA autoantibodies in B6C3F1 were not affected by TCE exposure. Overall, these data suggest that TCE did not contribute to the progression of autoimmune disease in autoimmune-prone mice during the period of 11-36 weeks of age, but rather lead to increased expression of markers associated with autoimmune disease in a non-genetically prone mouse strain.

  13. [Ketosis prone type 2 diabetes (KPD)].

    PubMed

    Concha L, Luciana; Durruty A, Pilar; García de Los Ríos A, Manuel

    2015-09-01

    Ketosis prone type 2 diabetes (KPD) is presently a well-defined clinical entity, characterized by a debut with severe hyperglycemia and ketoacidosis similar to the presenting form of Type 1 diabetes mellitus (DM1). However, it appears in subjects with Type 2 diabetes mellitus (DM2) phenotype. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. Once the acute stage subsides, patients behave as having a DM2 and do not require insulin treatment. They should be kept on a diet and oral hypoglycemic drugs due to their susceptibility to have recurrent acute ketotic decompensations.

  14. Extralevator abdominoperineal resection in the prone position.

    PubMed

    Flor-Lorente, Blas; Frasson, Matteo; Montilla, Erick

    2014-03-01

    The Miles operation is every day more in the limelight. The abdominoperineal resection compared to anterior resection results in increased rate of circumferential resection margin (CRM) infiltration, increased iatrogenic tumor perforation rate and poorer quality of the mesorectum. These worse results may be caused by excessive dissection between the distal mesorectum and the plane of the levator ani and the consequent "resection waist" or "cone" effect in the specimen. A wider excision of the pelvic floor muscles, known as extraelevator abdominoperineal resection (ELAPE), would provide a "cylindrical" specimen which would hypothetically reduce the risk of tumor perforation and CRM infiltration and local recurrence rate. However, there is insufficient evidence to conclude that the ELAPE is oncologically superior compared to standard abdominoperineal resection. Independently from the surgical technique adopted, another actual point of discussion is the position of the patient during the perineal part of the operation. The position on "prone" provides excellent pelvic exposure, a top-down dissection under direct vision and is very comfortable for the operating surgeons. However, there is no clear scientific evidence of the superiority of prone ELAPE over supine ELAPE in terms of oncologic results, morbidity and mortality. The laparoscopy seems to be the best surgical approach for the abdominal part of the operation, although it has not been validated so far by large prospective studies. Prospective, controlled and randomized trials are necessary to resolve all these issues. The current interest in a more accurate and standardized perineal surgery to obtain a cylindrical specimen, undoubtedly, will improve results.

  15. G-protein signaling modulator 1 deficiency accelerates cystic disease in an orthologous mouse model of autosomal dominant polycystic kidney disease.

    PubMed

    Kwon, Michelle; Pavlov, Tengis S; Nozu, Kandai; Rasmussen, Shauna A; Ilatovskaya, Daria V; Lerch-Gaggl, Alexandra; North, Lauren M; Kim, Hyunho; Qian, Feng; Sweeney, William E; Avner, Ellis D; Blumer, Joe B; Staruschenko, Alexander; Park, Frank

    2012-12-26

    Polycystic kidney diseases are the most common genetic diseases that affect the kidney. There remains a paucity of information regarding mechanisms by which G proteins are regulated in the context of polycystic kidney disease to promote abnormal epithelial cell expansion and cystogenesis. In this study, we describe a functional role for the accessory protein, G-protein signaling modulator 1 (GPSM1), also known as activator of G-protein signaling 3, to act as a modulator of cyst progression in an orthologous mouse model of autosomal dominant polycystic kidney disease (ADPKD). A complete loss of Gpsm1 in the Pkd1(V/V) mouse model of ADPKD, which displays a hypomorphic phenotype of polycystin-1, demonstrated increased cyst progression and reduced renal function compared with age-matched cystic Gpsm1(+/+) and Gpsm1(+/-) mice. Electrophysiological studies identified a role by which GPSM1 increased heteromeric polycystin-1/polycystin-2 ion channel activity via Gβγ subunits. In summary, the present study demonstrates an important role for GPSM1 in controlling the dynamics of cyst progression in an orthologous mouse model of ADPKD and presents a therapeutic target for drug development in the treatment of this costly disease.

  16. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  17. Loss of epidermal hypoxia-inducible factor-1α accelerates epidermal aging and affects re-epithelialization in human and mouse.

    PubMed

    Rezvani, Hamid Reza; Ali, Nsrein; Serrano-Sanchez, Martin; Dubus, Pierre; Varon, Christine; Ged, Cécile; Pain, Catherine; Cario-André, Muriel; Seneschal, Julien; Taïeb, Alain; de Verneuil, Hubert; Mazurier, Frédéric

    2011-12-15

    In mouse and human skin, HIF-1α is constitutively expressed in the epidermis, mainly in the basal layer. HIF-1α has been shown to have crucial systemic functions: regulation of kidney erythropoietin production in mice with constitutive HIF-1α epidermal deletion, and hypervascularity following epidermal HIF-1α overexpression. However, its local role in keratinocyte physiology has not been clearly defined. To address the function of HIF-1α in the epidermis, we used the mouse model of HIF-1α knockout targeted to keratinocytes (K14-Cre/Hif1a(flox/flox)). These mice had a delayed skin phenotype characterized by skin atrophy and pruritic inflammation, partly mediated by basement membrane disturbances involving laminin-332 (Ln-332) and integrins. We also investigated the relevance of results of studies in mice to human skin using reconstructed epidermis and showed that HIF-1α knockdown in human keratinocytes impairs the formation of a viable reconstructed epidermis. A diminution of keratinocyte growth potential, following HIF-1α silencing, was associated with a decreased expression of Ln-322 and α6 integrin and β1 integrin. Overall, these results indicate a role of HIF-1α in skin homeostasis especially during epidermal aging.

  18. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  19. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  20. Neglected Children, Shame-Proneness, and Depressive Symptoms

    PubMed Central

    Bennett, David S.; Sullivan, Margaret Wolan; Lewis, Michael

    2013-01-01

    Neglected children may be at increased risk for depressive symptoms. This study examines shame-proneness as an outcome of child neglect and as a potential explanatory variable in the relation between neglect and depressive symptoms. Participants were 111 children (52 with a Child Protective Services [CPS] allegation of neglect) seen at age 7. Neglected children reported more shame-proneness and more depressive symptoms than comparison children. Guilt-proneness, in contrast, was unrelated to neglect and depressive symptoms, indicating specificity for shame-proneness. The potential role of shame as a process variable that can help explain how some neglected children exhibit depressive symptoms is discussed. PMID:20724372

  1. Mouse mammary tumor virus infection accelerates mammary carcinogenesis in Wnt-1 transgenic mice by insertional activation of int-2/Fgf-3 and hst/Fgf-4.

    PubMed Central

    Shackleford, G M; MacArthur, C A; Kwan, H C; Varmus, H E

    1993-01-01

    Transgenic mice carrying the Wnt-1 protooncogene modified for expression in mammary epithelial cells exhibit hyperplastic mammary glands and stochastically develop mammary carcinomas, suggesting that additional events are necessary for tumorigenesis. To induce such events and to identify the genes involved, we have infected Wnt-1 transgenic mice with mouse mammary tumor virus (MMTV), intending to insertionally activate, and thereby molecularly tag, cooperating protooncogenes. Infection of breeding female Wnt-1 transgenics decreased the average age at which tumors appeared from approximately 4 months to approximately 2.5 months and increased the average number of primary tumors per mouse from 1-2 to > 5. A smaller effect was observed in virgin females, and infection of transgenic males showed no significant effect on tumor latency. More than half of the tumors from the infected breeding group contained one or more newly acquired MMTV proviruses in a pattern suggesting that most cells in tumors arose from a single infected cell. Analyses of provirus-containing tumors for induced or altered expression of int-2/Fgf-3, hst/Fgf-4, int-3, and Wnt-3 showed activation of int-2 in 39% of tumors, hst in 3%, and both int-2 and hst in 3%. DNA analyses with probes for protooncogenes and MMTV confirmed that the activations resulted from proviral insertions. There was no evidence for proviral insertions at the int-3, Wnt-3, or Wnt-1 loci. These findings provide further evidence that fibroblast growth factors Int-2 and Hst can cooperate with Wnt-1, another secreted factor, in mammary tumorigenesis, and they illustrate the capacity of this system to identify cooperating oncogenes. Images PMID:8380647

  2. Janus-faced Acrolein prevents allergy but accelerates tumor growth by promoting immunoregulatory Foxp3+ cells: Mouse model for passive respiratory exposure

    PubMed Central

    Roth-Walter, Franziska; Bergmayr, Cornelia; Meitz, Sarah; Buchleitner, Stefan; Stremnitzer, Caroline; Fazekas, Judit; Moskovskich, Anna; Müller, Mario A.; Roth, Georg A.; Manzano-Szalai, Krisztina; Dvorak, Zdenek; Neunkirchner, Alina; Jensen-Jarolim, Erika

    2017-01-01

    Acrolein, a highly reactive unsaturated aldehyde, is generated in large amounts during smoking and is best known for its genotoxic capacity. Here, we aimed to assess whether acrolein at concentrations relevant for smokers may also exert immunomodulatory effects that could be relevant in allergy or cancer. In a BALB/c allergy model repeated nasal exposure to acrolein abrogated allergen-specific antibody and cytokine formation, and led to a relative accumulation of regulatory T cells in the lungs. Only the acrolein-treated mice were protected from bronchial hyperreactivity as well as from anaphylactic reactions upon challenge with the specific allergen. Moreover, grafted D2F2 tumor cells grew faster and intratumoral Foxp3+ cell accumulation was observed in these mice compared to sham-treated controls. Results from reporter cell lines suggested that acrolein acts via the aryl-hydrocarbon receptor which could be inhibited by resveratrol and 3′-methoxy-4′-nitroflavone Acrolein- stimulation of human PBMCs increased Foxp3+ expression by T cells which could be antagonized by resveratrol. Our mouse and human data thus revealed that acrolein exerts systemic immunosuppression by promoting Foxp3+ regulatory cells. This provides a novel explanation why smokers have a lower allergy, but higher cancer risk. PMID:28332605

  3. Piezoelectric control of structures prone to instabilities

    NASA Astrophysics Data System (ADS)

    Kim, Sunjung

    Thin-walled structures such as stiffened panels fabricated out of high strength materials are ubiquitous in aerospace structures. These are prone to buckle in a variety of modes with strong possibility of adverse interaction under axial compression and/or bending. Optimally designed stiffened panels, at an appropriate combination of axial compression and suddenly applied lateral pressure undergo large amplitude oscillations and may experience divergence. Under aerodynamic loading, they can experience flutter instability with the amplitudes of oscillations attaining a limit (LCO) or escalating without any limit. Control of structures prone to these forms of instability using piezo-electric actuators is the theme of this dissertation. Issues involved in the control of stiffened panels under axial compression and liable to buckle simultaneously in local and overall modes are studied. The analytical approach employs finite elements in which are embedded periodic components of local buckling including the second order effects. It is shown that the adverse effects of mode interaction can be counteracted by simply controlling the overall bending of the stiffener by piezo-electric actuators attached its tips. Control is exercised by self-sensing actuators by direct negative feedback voltages proportional to the bending strains of the stiffener. In a dynamic loading environment, where vibrations are triggered by suddenly applied lateral pressure, negative velocity feedback is employed with voltages proportional to the bending strain-rate. The local plate oscillations are effectively controlled by a piezo-electric actuators placed along the longitudinal center line of the panel. The problem of flutter under aerodynamic pressure of stiffened panels in the linear and post-critical regimes is studied using modal analysis and finite strips. The analysis, control and interpretation of the response are facilitated by identification of two families of characteristic modes of

  4. Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8.

    PubMed

    Nakai, Megumi; Iizuka, Michiro; Matsui, Nobuaki; Hosogi, Kazuko; Imai, Akiko; Abe, Noriaki; Shiraishi, Hisashi; Hirata, Ayumu; Yagi, Yusuke; Jobu, Kohei; Yokota, Junko; Kato, Eishin; Hosoda, Shinya; Yoshioka, Saburo; Harada, Kenichi; Kubo, Miwa; Fukuyama, Yoshiyasu; Miyamura, Mitsuhiko

    2016-05-01

    Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.

  5. The effect of mycophenolate mofetil on disease development in the gld.apoE (-/-) mouse model of accelerated atherosclerosis and systemic lupus erythematosus.

    PubMed

    Richez, Christophe; Richards, Rocco J; Duffau, Pierre; Weitzner, Zachary; Andry, Christopher D; Rifkin, Ian R; Aprahamian, Tamar

    2013-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by autoantibody production and inflammatory disease involving multiple organs. Premature atherosclerosis is a common complication of SLE and results in substantial morbidity and mortality from cardiovascular disease (CVD). The reasons for the premature atherosclerosis in SLE are incompletely understood, although chronic inflammation is thought to play an important role. There is currently no known preventative treatment of premature atherosclerosis in SLE. Mycophenolate mofetil (MMF) is an immunosuppressive agent that is commonly used for treatment of patients with SLE. In order to study the impact of this drug on murine lupus disease including premature atherosclerosis development, we treated gld.apoE(-/-) mice, a model of SLE and accelerated atherosclerosis, with MMF. We maintained seven-week old gld.apoE(-/-) mice on a high cholesterol Western diet with or without MMF. After 12 weeks on diet, mice receiving MMF showed decreased atherosclerotic lesion area compared to the control group. MMF treatment also improved the lupus phenotype, indicated by a significant decrease circulating autoantibody levels and ameliorating lupus nephritis associated with this model. This data suggests that the effects of MMF on the immune system may not only be beneficial for lupus, but also for inflammation driving lupus-associated atherosclerosis.

  6. Interleukin-2 treatment reverses effects of cAMP-responsive element modulator α-over-expressing T cells in autoimmune-prone mice

    PubMed Central

    Ohl, K; Wiener, A; Schippers, A; Wagner, N; Tenbrock, K

    2015-01-01

    Systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), are often characterized by a failure of self-tolerance and result in an uncontrolled activation of B cells and effector T cells. Interleukin (IL)-2 critically maintains homeostasis of regulatory T cells (Treg) and effector T cells in the periphery. Previously, we identified the cAMP-responsive element modulator α (CREMα) as a major factor responsible for decreased IL-2 production in T cells from SLE patients. Additionally, using a transgenic mouse that specifically over-expresses CREMα in T cells (CD2CREMαtg), we provided in-vivo evidence that CREMα indeed suppresses IL-2 production. To analyse the effects of CREMα in an autoimmune prone mouse model we introduced a Fas mutation in the CD2CREMαtg mice (FVB/Fas–/–CD2CREMαtg). Overexpression of CREMα strongly accelerated the lymphadenopathy and splenomegaly in the FVB/Fas–/– mice. This was accompanied by a massive expansion of double-negative (DN) T cells, enhanced numbers of interferon (IFN)-γ-producing T cells and reduced percentages of Tregs. Treatment of FVB/Fas–/–CD2CREMαtg mice with IL-2 restored the percentage of Tregs and reversed increased IFN-γ production, but did not affect the number of DNTs. Our data indicate that CREMα contributes to the failure of tolerance in SLE by favouring effector T cells and decreasing regulatory T cells, partially mediated by repression of IL-2 in vivo. PMID:25817470

  7. Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a D-galactose-induced accelerated aging mouse model.

    PubMed

    Woo, Jae-Yeon; Gu, Wan; Kim, Kyung-Ah; Jang, Se-Eun; Han, Myung Joo; Kim, Dong-Hyun

    2014-06-01

    Aging is associated with Alzheimer's disease (AD), cardiovascular disease and cancer. Oxidative stress is considered as a major factor that accelerates the aging process. To understand the ability of lactic acid bacteria to ameliorate memory impairment caused by aging, we investigated the effect of Lactobacillus pentosus var. plantarum (C29), which is known to protect against scopolamine-induced memory impairment, on oxidative stress (D-galactose)-induced memory impairment in mice. D-Galactose was subcutaneously injected to 20-week old male C57BL/6J mice for 10 weeks, with oral administration of C29 for the final 5 weeks. Excessive intake of D-galactose not only impaired memory, which was indicated by passive avoidance, Y-maze, and Morris water-maze tasks, but also reduced the expression of brain-derived neurotrophic factor (BDNF) and hippocampal doublecortin (DCX) and the activation of cAMP response element-binding protein (CREB). C29 treatment ameliorated D-galactose-induced memory impairment and reversed the suppression of BDNF and DCX expression and CREB activation. Moreover, C29 decreased the expression of a senescence marker p16 and inflammation markers p-p65, p-FOXO3a, cyclooxygenase (COX)-2, and inducible NO synthase (iNOS). C29 treatment inhibited D-galactose-induced expression of M1 polarization markers tumor necrosis factor-α and arginase II, and attenuated the d-galactose-suppressed expression of M2 markers IL-10, arginase I and CD206. Taken together, these findings suggest that C29 may ameliorate memory impairment and M1 macrophage-polarized inflammation caused by aging.

  8. Enhanced growth of endothelial precursor cells on PCG-matrix facilitates accelerated, fibrosis-free, wound healing: a diabetic mouse model.

    PubMed

    Kanitkar, Meghana; Jaiswal, Amit; Deshpande, Rucha; Bellare, Jayesh; Kale, Vaijayanti P

    2013-01-01

    Diabetes mellitus (DM)-induced endothelial progenitor cell (EPC) dysfunction causes impaired wound healing, which can be rescued by delivery of large numbers of 'normal' EPCs onto such wounds. The principal challenges herein are (a) the high number of EPCs required and (b) their sustained delivery onto the wounds. Most of the currently available scaffolds either serve as passive devices for cellular delivery or allow adherence and proliferation, but not both. This clearly indicates that matrices possessing both attributes are 'the need of the day' for efficient healing of diabetic wounds. Therefore, we developed a system that not only allows selective enrichment and expansion of EPCs, but also efficiently delivers them onto the wounds. Murine bone marrow-derived mononuclear cells (MNCs) were seeded onto a PolyCaprolactone-Gelatin (PCG) nano-fiber matrix that offers a combined advantage of strength, biocompatibility wettability; and cultured them in EGM2 to allow EPC growth. The efficacy of the PCG matrix in supporting the EPC growth and delivery was assessed by various in vitro parameters. Its efficacy in diabetic wound healing was assessed by a topical application of the PCG-EPCs onto diabetic wounds. The PCG matrix promoted a high-level attachment of EPCs and enhanced their growth, colony formation, and proliferation without compromising their viability as compared to Poly L-lactic acid (PLLA) and Vitronectin (VN), the matrix and non-matrix controls respectively. The PCG-matrix also allowed a sustained chemotactic migration of EPCs in vitro. The matrix-effected sustained delivery of EPCs onto the diabetic wounds resulted in an enhanced fibrosis-free wound healing as compared to the controls. Our data, thus, highlight the novel therapeutic potential of PCG-EPCs as a combined 'growth and delivery system' to achieve an accelerated fibrosis-free healing of dermal lesions, including diabetic wounds.

  9. Regulation of the p19Arf/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice

    PubMed Central

    Soriano-Cantón, Raúl; Perez-Villalba, Ana; Morante-Redolat, José Manuel; Marqués-Torrejón, María Ángeles; Pallás, Mercé; Pérez-Sánchez, Francisco; Fariñas, Isabel

    2015-01-01

    Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1-NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age-related changes in B1-NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence-accelerated-prone mice (SAMP8) relative to senescence-accelerated-resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the study of aging. We have found that the B1-NSC compartment is transiently expanded in young SAMP8 relative to SAMR1 mice, resulting in disturbed cytoarchitecture of the SEZ, B1-NSC hyperproliferation, and higher yields of primary neurospheres. These unusual features are, however, accompanied by premature loss of B1-NSCs. Moreover, SAMP8 neurospheres lack self-renewal and enter p53-dependent senescence after only two passages. Interestingly, in vitro senescence of SAMP8 cells could be prevented by inhibition of histone acetyltransferases and mimicked in SAMR1 cells by inhibition of histone deacetylases (HDAC). Our data indicate that expression of the tumor suppressor p19, but not of p16, is increased in SAMP8 neurospheres, as well as in SAMR1 neurospheres upon HDAC inhibition, and suggest that the SAMP8 phenotype may, at least in part, be due to changes in chromatin status. Interestingly, acute HDAC inhibition in vivo resulted in changes in the SEZ of SAMR1 mice that resembled those found in young SAMP8 mice. PMID:25728253

  10. Dissociation and fantasy proneness in psychiatric patients: a preliminary study.

    PubMed

    Merckelbach, Harald; à Campo, Joost; Hardy, Solange; Giesbrecht, Timo

    2005-01-01

    Nonclinical studies found that dissociative experiences are intimately linked to a trait known as fantasy proneness. We examined the links among dissociative symptoms, fantasy proneness, and impulsivity in psychiatric outpatients. Our sample consisted of 22 patients with schizophrenia, 20 patients with a diagnosis of borderline personality disorder, and 19 patients with a major depressive disorder. For the whole sample, levels of dissociation were found to be related to fantasy proneness and impulsivity. There were group differences in dissociative symptoms, with patients with borderline personality disorder reporting more such symptoms than patients with either schizophrenia or major depressive disorder. The overlap between dissociation and fantasy proneness may have important ramifications for studies addressing comorbid phenomena of dissociative symptoms.

  11. Empathy, Guilt Proneness, and Gender: Relative Contributions to Prosocial Behaviour

    PubMed Central

    Torstveit, Linda; Sütterlin, Stefan; Lugo, Ricardo Gregorio

    2016-01-01

    Guilt is a moral emotion that is often looked upon as a negative trait. However, studies show that some individuals are more predisposed to think, feel and act in a more ethical manner because of a lower threshold to experience guilt. Some theories of helping behaviour emphasize the evolutionary mechanisms, while other theories stress the importance of social variables. This study investigated whether guilt proneness as a dispositional trait can be associated with prosocial behaviour. Five hundred sixty-nine participants reported in an online survey their own levels of guilt proneness, frequency of prosocial behaviour, and related cognitions such as empathy. This study is among the first to demonstrate how guilt proneness combined with empathy can explain additional variance in prosocial behaviour. The findings also indicate gender differences in the precursors of prosocial behaviour, suggesting women are more influenced by the effects of guilt proneness on prosocial behaviour than men. PMID:27298635

  12. Empathy, Guilt Proneness, and Gender: Relative Contributions to Prosocial Behaviour.

    PubMed

    Torstveit, Linda; Sütterlin, Stefan; Lugo, Ricardo Gregorio

    2016-05-01

    Guilt is a moral emotion that is often looked upon as a negative trait. However, studies show that some individuals are more predisposed to think, feel and act in a more ethical manner because of a lower threshold to experience guilt. Some theories of helping behaviour emphasize the evolutionary mechanisms, while other theories stress the importance of social variables. This study investigated whether guilt proneness as a dispositional trait can be associated with prosocial behaviour. Five hundred sixty-nine participants reported in an online survey their own levels of guilt proneness, frequency of prosocial behaviour, and related cognitions such as empathy. This study is among the first to demonstrate how guilt proneness combined with empathy can explain additional variance in prosocial behaviour. The findings also indicate gender differences in the precursors of prosocial behaviour, suggesting women are more influenced by the effects of guilt proneness on prosocial behaviour than men.

  13. Future accelerators (?)

    SciTech Connect

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  14. Mouse genetics: catalogue and scissors.

    PubMed

    Sung, Young Hoon; Baek, In-Jeoung; Seong, Je Kyung; Kim, Jin Soo; Lee, Han-Woong

    2012-12-01

    Phenotypic analysis of gene-specific knockout (KO) mice has revolutionized our understanding of in vivo gene functions. As the use of mouse embryonic stem (ES) cells is inevitable for conventional gene targeting, the generation of knockout mice remains a very time-consuming and expensive process. To accelerate the large-scale production and phenotype analyses of KO mice, international efforts have organized global consortia such as the International Knockout Mouse Consortium (IKMC) and International Mouse Phenotype Consortium (IMPC), and they are persistently expanding the KO mouse catalogue that is publicly available for the researches studying specific genes of interests in vivo. However, new technologies, adopting zinc-finger nucleases (ZFNs) or Transcription Activator-Like Effector (TALE) Nucleases (TALENs) to edit the mouse genome, are now emerging as valuable and effective shortcuts alternative for the conventional gene targeting using ES cells. Here, we introduce the recent achievement of IKMC, and evaluate the significance of ZFN/TALEN technology in mouse genetics.

  15. Death receptor 6 contributes to autoimmunity in lupus-prone mice

    PubMed Central

    Fujikura, Daisuke; Ikesue, Masahiro; Endo, Tsutomu; Chiba, Satoko; Higashi, Hideaki; Uede, Toshimitsu

    2017-01-01

    Expansion of autoreactive follicular helper T (Tfh) cells is tightly restricted to prevent induction of autoantibody-dependent immunological diseases, such as systemic lupus erythematosus (SLE). Here we show expression of an orphan immune regulator, death receptor 6 (DR6/TNFRSF21), on a population of Tfh cells that are highly expanded in lupus-like disease progression in mice. Genome-wide screening reveals an interaction between syndecan-1 and DR6 resulting in immunosuppressive functions. Importantly, syndecan-1 is expressed specifically on autoreactive germinal centre (GC) B cells that are critical for maintenance of Tfh cells. Syndecan-1 expression level on GC B cells is associated with Tfh cell expansion and disease progression in lupus-prone mouse strains. In addition, Tfh cell suppression by DR6-specific monoclonal antibody delays disease progression in lupus-prone mice. These findings suggest that the DR6/syndecan-1 axis regulates aberrant GC reactions and could be a therapeutic target for autoimmune diseases such as SLE. PMID:28045014

  16. The relationship between fantasy proneness and schizotypy in adolescents.

    PubMed

    Sánchez-Bernardos, María Luisa; Avia, María Dolores

    2006-06-01

    Previous research has found substantial relationships between fantasy proneness and schizotypy in adulthood. The aim of the present study is to examine the connections between these constructs in an adolescent sample. A sample of 511 adolescents filled out a measure of fantasy proneness and a measure of psychotic-like phenomena. The factorial pattern for schizotypal traits in adolescents replicate the earlier documented three-factor structure. Also, the full range of schizotypal features was found to be related to imaginative tendencies tapped by fantasy proneness. Finally, joint analysis of fantasy and schizotypy showed that, in adolescents, fantasy converges with magical ideation and the cognitive-perceptual dimension of schizotypy, but diverges from the interpersonal aspects of schizotypy.

  17. Right-frontal cortical asymmetry predicts increased proneness to nostalgia.

    PubMed

    Tullett, Alexa M; Wildschut, Tim; Sedikides, Constantine; Inzlicht, Michael

    2015-08-01

    Nostalgia is often triggered by feelings-such as sadness, loneliness, or meaninglessness-that are typically associated with withdrawal motivation. Here, we examined whether a trait tendency to experience withdrawal motivation is associated with nostalgia proneness. Past work indicates that baseline right-frontal cortical asymmetry is a neural correlate of withdrawal-related motivation. We therefore hypothesized that higher baseline levels of right-frontal asymmetry would predict increased proneness to nostalgia. We assessed participants' baseline levels of frontal cortical activity using EEG. Results supported the hypothesis and demonstrated that the association between relative right-frontal asymmetry and increased nostalgia remained significant when controlling for the Big Five personality traits. Overall, these findings indicate that individuals with a stronger dispositional tendency to experience withdrawal-related motivation are more prone to nostalgia.

  18. How to avoid perioperative visual loss following prone spinal surgery

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: In a prior article, “Perioperative visual loss (POVL) following prone spinal surgery: A review,” Epstein documented that postoperative visual loss (POVL) occurs in from 0.013% to 0.2% of spine procedures performed in the prone position. POVL is largely attributed to ischemic optic neuropathy (ION), central retinal artery occlusion (CRAO), cortical blindness (CB), direct compression (prone pillows/horseshoe, eye protectors), and rarely, acute angle closure glaucoma. Methods: Risk factors for ION include prolonged surgery, extensive fusions, anemia, hypotension, hypovolemia, diabetes, obesity, use of the Wilson frame, male sex, and microvascular pathology. CRAO may result from improper prone positioning (e.g., eye compression or rotation contributing to jugular/venous or carotid compression), while CB more typically results from both direct compression and obesity. Results: Several preventive/prophylactic measures should limit the risk of POVL. The routine use of an arterial line and continuous intraoperative monitoring document intraoperative hypotension/hypovolemia/anemia that can be immediately corrected with appropriate resuscitative measures. Application of a 3-pin head holder completely eliminates direct eye compression and maintains the neck in a neutral posture, thus avoiding rotation that can contribute to jugular/venous obstruction and/or inadvertent carotid compression. In addition, elevating the head 10° from the horizontal directly reduces intraocular pressure. Conclusions: The best way to avoid POVL following prone spine surgery is to prevent it. Routine use of an arterial line, intraoperative monitoring, a 3-pin head holder, and elevation of the head 10° from the horizontal should limit the risk of encountering POVL after spinal procedures performed in the prone position. PMID:27274406

  19. Hypnotic responsiveness: expectancy, attitudes, fantasy proneness, absorption, and gender.

    PubMed

    Green, Joseph P; Lynn, Steven Jay

    2011-01-01

    This study examines the effect of providing information linking participants' attitudes toward hypnosis with later hypnotic performance. Using total scale scores from McConkey's Opinions About Hypnosis scale, as well as subscale scores, the authors found a weak association between attitudes and performance among 460 student participants; however, the correlation was unaffected by prehypnotic information specifically connecting attitudes and performance. A brief, 3-item measure of hypnotic expectancies generated the strongest correlation with hypnotic responsiveness. The authors also found that the association between fantasy proneness and hypnotizability was unaffected by the order of scale administration. Finally, the study highlighted gender differences across measures of fantasy proneness, absorption, expectancy, and hypnotizability.

  20. Prone position in patients with acute respiratory distress syndrome

    PubMed Central

    Setten, Mariano; Plotnikow, Gustavo Adrián; Accoce, Matías

    2016-01-01

    Acute respiratory distress syndrome occupies a great deal of attention in intensive care units. Despite ample knowledge of the physiopathology of this syndrome, the focus in intensive care units consists mostly of life-supporting treatment and avoidance of the side effects of invasive treatments. Although great advances in mechanical ventilation have occurred in the past 20 years, with a significant impact on mortality, the incidence continues to be high. Patients with acute respiratory distress syndrome, especially the most severe cases, often present with refractory hypoxemia due to shunt, which can require additional treatments beyond mechanical ventilation, among which is mechanical ventilation in the prone position. This method, first recommended to improve oxygenation in 1974, can be easily implemented in any intensive care unit with trained personnel. Prone position has extremely robust bibliographic support. Various randomized clinical studies have demonstrated the effect of prone decubitus on the oxygenation of patients with acute respiratory distress syndrome measured in terms of the PaO2/FiO2 ratio, including its effects on increasing patient survival. The members of the Respiratory Therapists Committee of the Sociedad Argentina de Terapia Intensiva performed a narrative review with the objective of discovering the available evidence related to the implementation of prone position, changes produced in the respiratory system due to the application of this maneuver, and its impact on mortality. Finally, guidelines are suggested for decision-making. PMID:27925054

  1. The Validity and Utility of the Depression Proneness Rating Scale.

    ERIC Educational Resources Information Center

    Zemore, Robert; And Others

    The development of the Depression Proneness Rating Scale (DPRS) and three investigations into its reliability, validity, and factor structure are described. Subjects of all three studies were university undergraduates. The first study (n=100) found a stability coefficient of 0.82 for the DPRS over a test-retest (Time 1-Time 2) interval of 9 weeks.…

  2. Prone position in patients with acute respiratory distress syndrome.

    PubMed

    Setten, Mariano; Plotnikow, Gustavo Adrián; Accoce, Matías

    2016-01-01

    Acute respiratory distress syndrome occupies a great deal of attention in intensive care units. Despite ample knowledge of the physiopathology of this syndrome, the focus in intensive care units consists mostly of life-supporting treatment and avoidance of the side effects of invasive treatments. Although great advances in mechanical ventilation have occurred in the past 20 years, with a significant impact on mortality, the incidence continues to be high. Patients with acute respiratory distress syndrome, especially the most severe cases, often present with refractory hypoxemia due to shunt, which can require additional treatments beyond mechanical ventilation, among which is mechanical ventilation in the prone position. This method, first recommended to improve oxygenation in 1974, can be easily implemented in any intensive care unit with trained personnel. Prone position has extremely robust bibliographic support. Various randomized clinical studies have demonstrated the effect of prone decubitus on the oxygenation of patients with acute respiratory distress syndrome measured in terms of the PaO2/FiO2 ratio, including its effects on increasing patient survival. The members of the Respiratory Therapists Committee of the Sociedad Argentina de Terapia Intensiva performed a narrative review with the objective of discovering the available evidence related to the implementation of prone position, changes produced in the respiratory system due to the application of this maneuver, and its impact on mortality. Finally, guidelines are suggested for decision-making.

  3. The Social Antecedents of Anger Proneness in Young Adulthood

    ERIC Educational Resources Information Center

    Turner, R. Jay; Russell, David; Glover, Regan; Hutto, Pamela

    2007-01-01

    Anger has been shown to be an important factor in occupational maladjustment, family conflict, physical and sexual assault, criminal behavior, and substance abuse. It has also been linked with such adverse health outcomes as hypertension, heart disease, and cancer. Focusing on anger proneness, conceptualized as a relatively enduring propensity to…

  4. Pathogenesis of A-beta+ ketosis-prone diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A-beta+ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible beta-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnit...

  5. Prone position craniotomy in pregnancy without fetal heart rate monitoring.

    PubMed

    Jacob, Jean; Alexander, Ashish; Philip, Shoba; Thomas, Anoop

    2016-09-01

    A pregnant patient in second trimester scheduled for posterior fossa craniotomy in prone position is a challenge for the anesthesiologist. Things to consider are physiological changes during pregnancy, non-obstetric surgery in pregnant patients, neuroanesthetic principles, effects of prone positioning, and need for fetal heart rate (FHR) monitoring. We have described the anesthetic management of this case and discussed intra-operative FHR monitoring including controversies about its role, indications, and various options available as per fetal gestational age. In our case we attempted intermittent intra-operative FHR monitoring to optimize maternal positioning and fetal oxygenation even though the fetus was pre-viable. However the attempt was abandoned due to practical difficulties with prone positioning. Patient made good neurological recovery following the procedure and delivered a healthy term baby 4 months later. Decisions regarding fetal monitoring should be individualized based on viability of the fetus and feasibility of emergency cesarean delivery. Good communication between a multidisciplinary team involving neurosurgeon, anesthesiologist, obstetrician, and neonatologist is important for a successful outcome for mother and fetus. We conclude that prone position neurosurgery can safely be carried out in a pregnant patient with pre-viable fetus without FHR monitoring.

  6. LINEAR ACCELERATOR

    DOEpatents

    Colgate, S.A.

    1958-05-27

    An improvement is presented in linear accelerators for charged particles with respect to the stable focusing of the particle beam. The improvement consists of providing a radial electric field transverse to the accelerating electric fields and angularly introducing the beam of particles in the field. The results of the foregoing is to achieve a beam which spirals about the axis of the acceleration path. The combination of the electric fields and angular motion of the particles cooperate to provide a stable and focused particle beam.

  7. Perioperative visual loss following prone spinal surgery: A review

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: Postoperative visual loss (POVL) following prone spine surgery occurs in from 0.013% to 1% of cases and is variously attributed to ischemic optic neuropathy (ION: anterior ION or posterior ION [reported in 1.9/10,000 cases: constitutes 89% of all POVL cases], central retinal artery occlusion [CRAO], central retinal vein occlusion [CRVO], cortical blindness [CB], direct compression [horseshoe, prone pillows, and eye protectors Dupaco Opti-Gard]), and acute angle closure glaucoma (AACG). Methods: Risk factors for ION include prolonged operative times, long-segment spinal instrumentation, anemia, intraoperative hypotension, diabetes, obesity, male sex, using the Wilson frame, microvascular pathology, decreased the percent of colloid administration, and extensive intraoperative blood loss. Risk factors for CRAO more typically include improper positioning during the surgery (e.g., cervical rotation), while those for CB included prone positioning and obesity. Results: POVL may be avoided by greater utilization of crystalloids versus colloids, administration of α-2 agonists (e.g., decreases intraocular pressure), avoidance of catecholamines (e.g., avoid vasoconstrictors), avoiding intraoperative hypotension, and averting anemia. Patients with glaucoma or glaucoma suspects may undergo preoperative evaluation by ophthalmologists to determine whether they require prophylactic treatment prior to prone spinal surgery and whether and if prophylactic treatment is warranted. Conclusions: The best way to avoid POVL is to recognize its multiple etiologies and limit the various risk factors that contribute to this devastating complication of prone spinal surgery. Furthermore, routinely utilizing a 3-pin head holder will completely avoid ophthalmic compression, while maintaining the neck in a neutral posture, largely avoiding the risk of jugular vein and/or carotid artery compromise and thus avoiding increasing IOP. PMID:27274409

  8. Acceleration switch

    DOEpatents

    Abbin, Jr., Joseph P.; Devaney, Howard F.; Hake, Lewis W.

    1982-08-17

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  9. Acceleration switch

    DOEpatents

    Abbin, J.P. Jr.; Devaney, H.F.; Hake, L.W.

    1979-08-29

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  10. ION ACCELERATOR

    DOEpatents

    Bell, J.S.

    1959-09-15

    An arrangement for the drift tubes in a linear accelerator is described whereby each drift tube acts to shield the particles from the influence of the accelerating field and focuses the particles passing through the tube. In one embodiment the drift tube is splii longitudinally into quadrants supported along the axis of the accelerator by webs from a yoke, the quadrants. webs, and yoke being of magnetic material. A magnetic focusing action is produced by energizing a winding on each web to set up a magnetic field between adjacent quadrants. In the other embodiment the quadrants are electrically insulated from each other and have opposite polarity voltages on adjacent quadrants to provide an electric focusing fleld for the particles, with the quadrants spaced sufficienily close enough to shield the particles within the tube from the accelerating electric field.

  11. Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

    PubMed Central

    Fujitsuka, N; Asakawa, A; Morinaga, A; Amitani, M S; Amitani, H; Katsuura, G; Sawada, Y; Sudo, Y; Uezono, Y; Mochiki, E; Sakata, I; Sakai, T; Hanazaki, K; Yada, T; Yakabi, K; Sakuma, E; Ueki, T; Niijima, A; Nakagawa, K; Okubo, N; Takeda, H; Asaka, M; Inui, A

    2016-01-01

    Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP–CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan. PMID:26830139

  12. LINEAR ACCELERATOR

    DOEpatents

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  13. Pristane-Accelerated Autoimmune Disease in (SWR X NZB) F1 Mice Leads to Prominent Tubulointerstitial Inflammation and Human Lupus Nephritis-Like Fibrosis

    PubMed Central

    Gardet, Agnes; Chou, Wei C.; Reynolds, Taylor L.; Velez, Diana B.; Fu, Kai; Czerkowicz, Julia M.; Bajko, Jeffrey; Ranger, Ann M.; Allaire, Normand; Kerns, Hannah M.; Ryan, Sarah; Legault, Holly M.; Dunstan, Robert W.; Lafyatis, Robert; Lukashev, Matvey; Viney, Joanne L.; Browning, Jeffrey L.; Rabah, Dania

    2016-01-01

    Mouse models lupus nephritis (LN) have provided important insights into disease pathogenesis, although none have been able to recapitulate all features of the human disease. Using comprehensive longitudinal analyses, we characterized a novel accelerated mouse model of lupus using pristane treatment in SNF1 (SWR X NZB F1) lupus prone mice (pristane-SNF1 mice). Pristane treatment in SNF1 mice accelerated the onset and progression of proteinuria, autoantibody production, immune complex deposition and development of renal lesions. At week 14, the pristane-SNF1 model recapitulated kidney disease parameters and molecular signatures seen in spontaneous disease in 36 week-old SNF1 mice and in a traditional IFNα-accelerated NZB X NZW F1 (BWF1) model. Blood transcriptome analysis revealed interferon, plasma cell, neutrophil, T-cell and protein synthesis signatures in the pristane-SNF1 model, all known to be present in the human disease. The pristane-SNF1 model appears to be particularly useful for preclinical research, robustly exhibiting many characteristics reminiscent of human disease. These include i) a stronger upregulation of the cytosolic nucleic acid sensing pathway, which is thought to be key component of the pathogenesis of the human disease, and ii) more prominent kidney interstitial inflammation and fibrosis, which have been both associated with poor prognosis in human LN. To our knowledge, this is the only accelerated model of LN that exhibits a robust tubulointerstitial inflammatory and fibrosis response. Taken together our data show that the pristane-SNF1 model is a novel accelerated model of LN with key features similar to human disease. PMID:27760209

  14. Enhancing disaster management by mapping disaster proneness and preparedness.

    PubMed

    Mishra, Vishal; Fuloria, Sanjay; Bisht, Shailendra Singh

    2012-07-01

    The focus of most disaster management programmes is to deploy resources-physical and human-from outside the disaster zone. This activity can produce a delay in disaster mitigation and recovery efforts, and a consequent loss of human lives and economic resources. It may be possible to expedite recovery and prevent loss of life by mapping out disaster proneness and the availability of resources in advance. This study proposes the development of two indices to do so. The Indian census data of 2001 is used to develop a methodology for creating one index on disaster proneness and one on resourcefulness for administrative units (tehsils). Findings reveal that tehsil residents face an elevated risk of disaster and that they are also grossly under-prepared for such events. The proposed indices can be used to map regional service provision facilities and to assist authorities in evaluating immediate, intermediate, and long-term disaster recovery needs and resource requirements.

  15. Symmetric Biomechanically Guided Prone-to-Supine Breast Image Registration.

    PubMed

    Eiben, Björn; Vavourakis, Vasileios; Hipwell, John H; Kabus, Sven; Buelow, Thomas; Lorenz, Cristian; Mertzanidou, Thomy; Reis, Sara; Williams, Norman R; Keshtgar, Mohammed; Hawkes, David J

    2016-01-01

    Prone-to-supine breast image registration has potential application in the fields of surgical and radiotherapy planning, image guided interventions, and multi-modal cancer diagnosis, staging, and therapy response prediction. However, breast image registration of three dimensional images acquired in different patient positions is a challenging problem, due to large deformations induced to the soft breast tissue caused by the change in gravity loading. We present a symmetric, biomechanical simulation based registration framework which aligns the images in a central, virtually unloaded configuration. The breast tissue is modelled as a neo-Hookean material and gravity is considered as the main source of deformation in the original images. In addition to gravity, our framework successively applies image derived forces directly into the unloading simulation in place of a subsequent image registration step. This results in a biomechanically constrained deformation. Using a finite difference scheme avoids an explicit meshing step and enables simulations to be performed directly in the image space. The explicit time integration scheme allows the motion at the interface between chest and breast to be constrained along the chest wall. The feasibility and accuracy of the approach presented here was assessed by measuring the target registration error (TRE) using a numerical phantom with known ground truth deformations, nine clinical prone MRI and supine CT image pairs, one clinical prone-supine CT image pair and four prone-supine MRI image pairs. The registration reduced the mean TRE for the numerical phantom experiment from initially 19.3 to 0.9 mm and the combined mean TRE for all fourteen clinical data sets from 69.7 to 5.6 mm.

  16. Evaluating fatigue in lupus-prone mice: preliminary assessments.

    PubMed

    Meeks, Allison; Larson, Susan J

    2012-01-01

    Fatigue is a debilitating condition suffered by many as the result of chronic disease, yet relatively little is known about its biological basis or how to effectively manage its effects. This study sought to evaluate chronic fatigue by using lupus-prone mice and testing them at three different time periods. Lupus-prone mice were chosen because fatigue affects over half of patients with Systemic Lupus Erythematosus. Eleven MLR⁺/(+) (genetic controls) and twelve MLR/MpJ-Fas/J (MRL/lpr; lupus-prone) mice were tested three times: once at 12, 16 and 20 weeks of age. All mice were subjected to a variety of behavioral tests including: forced swim, post-swim grooming, running wheel, and sucrose consumption; five of the MLR⁺/(+) and five of the MLR/lpr mice were also tested on a fixed ratio-25 operant conditioning task. MRL/lpr mice showed more peripheral symptoms of lupus than controls, particularly lymphadenopathy and proteinuria. Lupus mice spent more time floating during the forced swim test and traveled less distance in the running wheel at each testing period. There were no differences between groups in post-swim grooming or in number of reinforcers earned in the operant conditioning task indicating the behavioral changes were not likely due simply to muscle weakness or motivation. Correlations between performance in the running wheel, forced swim test and sucrose consumption were conducted and distance traveled in the running wheel was consistently negatively correlated with time spent floating. Based on these data, we conclude that the lupus-prone mice were experiencing chronic fatigue and that running wheel activity and floating during a forced swim test can be used to evaluate fatigue, although these data cannot rule out the possibility that both fatigue and a depressive-like state were mediating these effects.

  17. Prone positioning reduces severe pushing behavior: three case studies

    PubMed Central

    Fujino, Yuji; Amimoto, Kazu; Sugimoto, Satoshi; Fukata, Kazuhiro; Inoue, Masahide; Takahashi, Hidetoshi; Makita, Shigeru

    2016-01-01

    [Purpose] Pushing behavior is classically described as a disorder of body orientation in the coronal plane. Most interventions for pushing behavior have focused on correcting the deviation in vertical perception. However, pushing behavior seems to involve erroneous movements associated with excessive motor output by the non-paretic limbs and trunk. The present study aimed to inhibit muscular hyper-activity by placing the non-paretic limbs and trunk in the prone position. [Subjects and Methods] The subjects of the present study were 3 acute stroke patients with severe pushing behavior. The study consisted of the following 3 phases: baseline, intervention, and follow-up. In addition to conventional therapy, patients received relaxation therapy in the prone position for 10 minutes a day over 2 days. The severity of pushing behavior was assessed using the scale for contraversive pushing, and truncal balance was evaluated using the trunk control test. These assessments were performed before and after the baseline phase, and after the intervention and follow-up phases. [Results] At the baseline phase, both scores were poor. Both scores improved after the intervention and follow-up phases, and all the patients could sit independently. [Conclusion] Relaxation therapy in the prone position might ameliorate pushing behavior and impaired truncal balance. PMID:27799722

  18. Acceleration Studies

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.

    1993-01-01

    Work to support the NASA MSFC Acceleration Characterization and Analysis Project (ACAP) was performed. Four tasks (analysis development, analysis research, analysis documentation, and acceleration analysis) were addressed by parallel projects. Work concentrated on preparation for and implementation of near real-time SAMS data analysis during the USMP-1 mission. User support documents and case specific software documentation and tutorials were developed. Information and results were presented to microgravity users. ACAP computer facilities need to be fully implemented and networked, data resources must be cataloged and accessible, future microgravity missions must be coordinated, and continued Orbiter characterization is necessary.

  19. Musical Electroacupuncture May Be a Better Choice than Electroacupuncture in a Mouse Model of Alzheimer's Disease

    PubMed Central

    Jiang, Jing; Liu, Gang

    2016-01-01

    Objectives. To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer's disease. Methods. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer's disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer's disease (AD), and normal (N) groups were assessed. Results. The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and Aβ amyloid content in the frontal lobe, compared with the AD group (P < 0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD. Conclusion. MEA therapy may be superior to EA in treating Alzheimer's disease as demonstrated in SAMP8 mice. PMID:27974974

  20. Pathogenesis of A⁻β⁺ ketosis-prone diabetes.

    PubMed

    Patel, Sanjeet G; Hsu, Jean W; Jahoor, Farook; Coraza, Ivonne; Bain, James R; Stevens, Robert D; Iyer, Dinakar; Nalini, Ramaswami; Ozer, Kerem; Hampe, Christiane S; Newgard, Christopher B; Balasubramanyam, Ashok

    2013-03-01

    A⁻β⁺ ketosis-prone diabetes (KPD) is an emerging syndrome of obesity, unprovoked ketoacidosis, reversible β-cell dysfunction, and near-normoglycemic remission. We combined metabolomics with targeted kinetic measurements to investigate its pathophysiology. Fasting plasma fatty acids, acylcarnitines, and amino acids were quantified in 20 KPD patients compared with 19 nondiabetic control subjects. Unique signatures in KPD--higher glutamate but lower glutamine and citrulline concentrations, increased β-hydroxybutyryl-carnitine, decreased isovaleryl-carnitine (a leucine catabolite), and decreased tricarboxylic acid (TCA) cycle intermediates--generated hypotheses that were tested through stable isotope/mass spectrometry protocols in nine new-onset, stable KPD patients compared with seven nondiabetic control subjects. Free fatty acid flux and acetyl CoA flux and oxidation were similar, but KPD had slower acetyl CoA conversion to β-hydroxybutyrate; higher fasting β-hydroxybutyrate concentration; slower β-hydroxybutyrate oxidation; faster leucine oxidative decarboxylation; accelerated glutamine conversion to glutamate without increase in glutamate carbon oxidation; and slower citrulline flux, with diminished glutamine amide-nitrogen transfer to citrulline. The confluence of metabolomic and kinetic data indicate a distinctive pathogenic sequence: impaired ketone oxidation and fatty acid utilization for energy, leading to accelerated leucine catabolism and transamination of α-ketoglutarate to glutamate, with impaired TCA anaplerosis of glutamate carbon. They highlight a novel process of defective energy production and ketosis in A⁻β⁺ KPD.

  1. TACI-dependent APRIL signaling maintains autoreactive B cells in a mouse model of systemic lupus erythematosus.

    PubMed

    Tran, Ngoc Lan; Schneider, Pascal; Santiago-Raber, Marie-Laure

    2017-03-07

    Autoantibodies contribute to the development of Systemic Lupus Erythematosus (SLE). APRIL (a proliferation-inducing ligand), a member of the TNF superfamily, regulates plasma-cell survival and binds to TACI (transmembrane activator CAML interactor) and BCMA (B cell maturation antigen). We previously showed that APRIL blockade delayed disease onset in lupus-prone mice. In order to evaluate the role of APRIL receptors in the development of SLE, APRIL, TACI, BCMA or double TACI.BCMA null mutations were introduced into the Nba2.Yaa spontaneous lupus mouse model. Mortality as a consequence of Glomerulonephritis (GN) was reduced in Nba2.APRIL(-/-) .Yaa, Nba2.TACI(-/-) .Yaa and double-KO mice compared with Nba2.Yaa mice and correlated with lower levels of circulating antibodies, while splenic populations remained unchanged. In contrast, the appearance of symptoms was accelerated in BCMA-deficient mice, in which TACI signaling was increased. Finally, lupus-prone mice deficient for the APRIL-TACI axis produced less pathogenic antibodies and developed less GN. Disease reduction was attributed to impaired T-independent type 2 responses when the APRIL-TACI signaling axis was disrupted. Collectively, our results have identified and confirmed APRIL as a new target involved in B-cell activation, in the maintenance of plasma cell survival and subsequent increased autoantibody production that sustains lupus development in mice. This article is protected by copyright. All rights reserved.

  2. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  3. Plasma accelerator

    DOEpatents

    Wang, Zhehui; Barnes, Cris W.

    2002-01-01

    There has been invented an apparatus for acceleration of a plasma having coaxially positioned, constant diameter, cylindrical electrodes which are modified to converge (for a positive polarity inner electrode and a negatively charged outer electrode) at the plasma output end of the annulus between the electrodes to achieve improved particle flux per unit of power.

  4. Accelerated Achievement

    ERIC Educational Resources Information Center

    Ford, William J.

    2010-01-01

    This article focuses on the accelerated associate degree program at Ivy Tech Community College (Indiana) in which low-income students will receive an associate degree in one year. The three-year pilot program is funded by a $2.3 million grant from the Lumina Foundation for Education in Indianapolis and a $270,000 grant from the Indiana Commission…

  5. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  6. History of landslide susceptibility and a chorology of landslide-prone areas in the Western Ghats of Kerala, India

    NASA Astrophysics Data System (ADS)

    Kuriakose, Sekhar L.; Sankar, G.; Muraleedharan, C.

    2009-06-01

    Kerala is the third most densely populated state in India. It is a narrow strip of land, of which 47% is occupied by the most prominent orographic feature of peninsular India, The Western Ghats mountain chain. The highlands of Kerala experience several types of landslides, of which debris flows are the most common. They are called “Urul Pottal” in the local vernacular. The west-facing Western Ghats scarps that runs the entire extent of the mountain system is the most prone physiographic unit for landslides. The highlands of the region experience an annual average rainfall as high as 500 cm through the South-West, North-East and Pre-Monsoon showers. A survey of ancient documents and early news papers indicates a reduced rate of slope instability in the past. The processes leading to landslides were accelerated by anthropogenic disturbances such as deforestation since the early 18th century, terracing and obstruction of ephemeral streams and cultivation of crops lacking capability to add root cohesion in steep slopes. The events have become more destructive given the increasing vulnerability of population and property. Majority of mass movements have occurred in hill slopes >20° along the Western Ghats scarps, the only exception being the coastal cliffs. Studies conducted in the state indicates that prolonged and intense rainfall or more particularly a combination of the two and the resultant pore pressure variations are the most important trigger of landslides. The initiation zone of most of the landslides was typical hollows generally having degraded natural vegetation. A survey of post-landslide investigation and news paper reports enabled the identification of 29 major landslide events in the state. All except one of the 14 districts in the state are prone to landslides. Wayanad and Kozhikode districts are prone to deep seated landslides, while Idukki and Kottayam are prone to shallow landslides.

  7. 44 CFR 60.22 - Planning considerations for flood-prone areas.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Planning considerations for...., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.22 Planning considerations for flood-prone areas.... In the event of an overall drainage basin plan, provide that the flood carrying capacity within...

  8. Reduced nursing frequency during prolonged lactation in the mouse decreases milk production and increases mammary expression of tryptophan hydroxylase 1 (TPH1), but does not accelerate mammary gland remodeling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have observed that lactating mouse dams nursed 4 times per day (4X) maintained lactation, but had lower milk yields by the weigh-suckle-weigh method, than dams nursed ad libitum (AL). Therefore, we hypothesized that decreased nursing frequency would also decrease lactation persistence, increase m...

  9. Particle Accelerators in China

    NASA Astrophysics Data System (ADS)

    Zhang, Chuang; Fang, Shouxian

    As the special machines that can accelerate charged particle beams to high energy by using electromagnetic fields, particle accelerators have been widely applied in scientific research and various areas of society. The development of particle accelerators in China started in the early 1950s. After a brief review of the history of accelerators, this article describes in the following sections: particle colliders, heavy-ion accelerators, high-intensity proton accelerators, accelerator-based light sources, pulsed power accelerators, small scale accelerators, accelerators for applications, accelerator technology development and advanced accelerator concepts. The prospects of particle accelerators in China are also presented.

  10. Size and Shape Analysis of Error-Prone Shape Data

    PubMed Central

    Du, Jiejun; Dryden, Ian L.; Huang, Xianzheng

    2015-01-01

    We consider the problem of comparing sizes and shapes of objects when landmark data are prone to measurement error. We show that naive implementation of ordinary Procrustes analysis that ignores measurement error can compromise inference. To account for measurement error, we propose the conditional score method for matching configurations, which guarantees consistent inference under mild model assumptions. The effects of measurement error on inference from naive Procrustes analysis and the performance of the proposed method are illustrated via simulation and application in three real data examples. Supplementary materials for this article are available online. PMID:26109745

  11. Compact accelerator

    DOEpatents

    Caporaso, George J.; Sampayan, Stephen E.; Kirbie, Hugh C.

    2007-02-06

    A compact linear accelerator having at least one strip-shaped Blumlein module which guides a propagating wavefront between first and second ends and controls the output pulse at the second end. Each Blumlein module has first, second, and third planar conductor strips, with a first dielectric strip between the first and second conductor strips, and a second dielectric strip between the second and third conductor strips. Additionally, the compact linear accelerator includes a high voltage power supply connected to charge the second conductor strip to a high potential, and a switch for switching the high potential in the second conductor strip to at least one of the first and third conductor strips so as to initiate a propagating reverse polarity wavefront(s) in the corresponding dielectric strip(s).

  12. Laser acceleration

    NASA Astrophysics Data System (ADS)

    Tajima, T.; Nakajima, K.; Mourou, G.

    2017-02-01

    The fundamental idea of Laser Wakefield Acceleration (LWFA) is reviewed. An ultrafast intense laser pulse drives coherent wakefield with a relativistic amplitude robustly supported by the plasma. While the large amplitude of wakefields involves collective resonant oscillations of the eigenmode of the entire plasma electrons, the wake phase velocity ˜ c and ultrafastness of the laser pulse introduce the wake stability and rigidity. A large number of worldwide experiments show a rapid progress of this concept realization toward both the high-energy accelerator prospect and broad applications. The strong interest in this has been spurring and stimulating novel laser technologies, including the Chirped Pulse Amplification, the Thin Film Compression, the Coherent Amplification Network, and the Relativistic Mirror Compression. These in turn have created a conglomerate of novel science and technology with LWFA to form a new genre of high field science with many parameters of merit in this field increasing exponentially lately. This science has triggered a number of worldwide research centers and initiatives. Associated physics of ion acceleration, X-ray generation, and astrophysical processes of ultrahigh energy cosmic rays are reviewed. Applications such as X-ray free electron laser, cancer therapy, and radioisotope production etc. are considered. A new avenue of LWFA using nanomaterials is also emerging.

  13. BICEP's acceleration

    SciTech Connect

    Contaldi, Carlo R.

    2014-10-01

    The recent Bicep2 [1] detection of, what is claimed to be primordial B-modes, opens up the possibility of constraining not only the energy scale of inflation but also the detailed acceleration history that occurred during inflation. In turn this can be used to determine the shape of the inflaton potential V(φ) for the first time — if a single, scalar inflaton is assumed to be driving the acceleration. We carry out a Monte Carlo exploration of inflationary trajectories given the current data. Using this method we obtain a posterior distribution of possible acceleration profiles ε(N) as a function of e-fold N and derived posterior distributions of the primordial power spectrum P(k) and potential V(φ). We find that the Bicep2 result, in combination with Planck measurements of total intensity Cosmic Microwave Background (CMB) anisotropies, induces a significant feature in the scalar primordial spectrum at scales k∼ 10{sup -3} Mpc {sup -1}. This is in agreement with a previous detection of a suppression in the scalar power [2].

  14. Changes in nerve- and endothelium-mediated contractile tone of the corpus cavernosum in a mouse model of pre-mature ageing.

    PubMed

    Lafuente-Sanchis, A; Triguero, D; Garcia-Pascual, A

    2014-07-01

    Erectile dysfunction (ED) is very prevalent in the older population, although the ageing-related mechanisms involved in the development of ED are poorly understood. We propose that age-induced differences in nerve- and endothelium-mediated smooth muscle contractility in the corpus cavernosum (CC) could be found between a senescent-accelerated mouse prone (SAMP8) and senescent-accelerated mouse resistant (SAMR1) strains. We analysed the changes in muscle tension induced by electrical field stimulation (EFS) or agonist addition 'in vitro', assessing nerve density (adrenergic, cholinergic and nitrergic), the expression of endothelial nitric oxide synthase (eNOS), cGMP accumulation and the distribution of interstitial cells (ICs) by immunofluorescence. We observed no change in both the nerve-dependent adrenergic excitatory contractility at physiological levels of stimulation and in the nitrergic inhibitory response in SAMP8 animals. Unlike cholinergic innervation, the density of adrenergic and nitrergic nerves increased in SAMP8 mice. In contrast, smooth muscle sensitivity to exogenous noradrenaline (NA) was slightly reduced, whereas cGMP accumulation in response to EFS and DEA/NO, and relaxations to DEA/NO and sildenafil, were not modified. No changes in the expression of eNOS and in the distribution of vimentin-positive ICs were detected in the aged animals. The ACh induced atropine-sensitive biphasic endothelium-dependent responses involved relaxation at low concentrations that turned into contractions at the highest doses. CC relaxation was mainly because of the production of NO together with some relaxant prostanoid, which did not change in SAMP8 animals. In contrast, the contractile component was considerably higher in the aged animals and it was completely inhibited by indomethacin. In conclusion, a clear imbalance towards enhanced production of contractile prostanoids from the endothelium may contribute to ED in the elderly. On the basis of these data, we

  15. Mouse models in oncoimmunology.

    PubMed

    Zitvogel, Laurence; Pitt, Jonathan M; Daillère, Romain; Smyth, Mark J; Kroemer, Guido

    2016-12-01

    Fundamental cancer research and the development of efficacious antineoplastic treatments both rely on experimental systems in which the relationship between malignant cells and immune cells can be studied. Mouse models of transplantable, carcinogen-induced or genetically engineered malignancies - each with their specific advantages and difficulties - have laid the foundations of oncoimmunology. These models have guided the immunosurveillance theory that postulates that evasion from immune control is an essential feature of cancer, the concept that the long-term effects of conventional cancer treatments mostly rely on the reinstatement of anticancer immune responses and the preclinical development of immunotherapies, including currently approved immune checkpoint blockers. Specific aspects of pharmacological development, as well as attempts to personalize cancer treatments using patient-derived xenografts, require the development of mouse models in which murine genes and cells are replaced with their human equivalents. Such 'humanized' mouse models are being progressively refined to characterize the leukocyte subpopulations that belong to the innate and acquired arms of the immune system as they infiltrate human cancers that are subjected to experimental therapies. We surmise that the ever-advancing refinement of murine preclinical models will accelerate the pace of therapeutic optimization in patients.

  16. [Reactance proneness, collectivism, uniqueness, and resistance to persuasion].

    PubMed

    Imajo, Shuzo

    2002-10-01

    This study examined the reliability and validity of Japanese psychological reactance scales. A total of 167 undergraduates completed a questionnaire of Therapeutic Reactance Scale (TRS), the Hong Reactance Scale (HRS), the Uniqueness Scale, and the Collectivism Scale. They also received messages involving three persuasion situations that were either high or low in terms of threat, and were asked to describe their reactions to them. The author categorized the reactions into three: acceptance, indirect resistance, and direct resistance. Reliabilities of the reactance scales were satisfactory. Their scores positively correlated with uniqueness scores, and negatively with collectivism scores. Those high on reactance proneness were less persuaded in two of the three situations. But in the third, an HRS by threat interaction was observed, indicating that only those who were high on reactance proneness under the high-threat condition showed resistance to persuasion. These results suggest that the Japanese versions of reactance scale were reliable and valid. However, the assertiveness aspect of TRS may not be appropriate for the definition of reactance. The influence of culture on psychological reactance was also discussed.

  17. Study on proneness of spontaneous combustion of macerals

    SciTech Connect

    Zhang, Y.G.; Li, F.; Tang, X.Y.; Xie, K.C.

    1999-07-01

    Pure macerals from brown coal to gas coal were separated from coalfields of Pingzhuang, Liaoyuan, Fuxin, Fushun, Changguang Hunyuan and Tangcun, and effect of macerals on spontaneous combustion was recently investigated with ignition temperature and index gas technique. Three kinds of maceral group with same rank have different ignition temperature and proneness of spontaneous combustion. Vitrinite group has the lowest ignition temperature, it is the most liable to spontaneous combustion, and the proneness of spontaneous combustion of coal increases with the increases of vitrain content, fusinite group has the highest ignition temperature, is least liable; Exinite group is in the middle. Gaseous products of three kinds of maceral group such as CO, C{sub 2}H{sub 4} and C{sub 3}H{sub 6} which are used as index gas have different rates of formation during oxidation; the vitrinite group is higher than others. Vitrinite group with more active site is easy to oxidize at low temperature. Exinite group with the lowest aromaticity and many aliphatic structure present in the aromatic layers is of steady chemical properties, so it is least liable to oxidize at low temperature. Fusinite group with the short CH{sub 3} and/or CH{sub 2} side chain and fewer active sites in the aromatic rings is inert in chemical properties and most difficult to oxidize at low temperature.

  18. Mouse genetics: Catalogue and scissors

    PubMed Central

    Sung, Young Hoon; Baek, In-Jeoung; Seong, Je Kyung; Kim, Jin-Soo; Lee, Han-Woong

    2012-01-01

    Phenotypic analysis of gene-specific knockout (KO) mice has revolutionized our understanding of in vivo gene functions. As the use of mouse embryonic stem (ES) cells is inevitable for conventional gene targeting, the generation of knockout mice remains a very time-consuming and expensive process. To accelerate the large-scale production and phenotype analyses of KO mice, international efforts have organized global consortia such as the International Knockout Mouse Consortium (IKMC) and International Mouse Phenotype Consortium (IMPC), and they are persistently expanding the KO mouse catalogue that is publicly available for the researches studying specific genes of interests in vivo. However, new technologies, adopting zinc-finger nucleases (ZFNs) or Transcription Activator-Like Effector (TALE) Nucleases (TALENs) to edit the mouse genome, are now emerging as valuable and effective shortcuts alternative for the conventional gene targeting using ES cells. Here, we introduce the recent achievement of IKMC, and evaluate the significance of ZFN/TALEN technology in mouse genetics. [BMB Reports 2012; 45(12): 686-692] PMID:23261053

  19. Advanced concepts for acceleration

    SciTech Connect

    Keefe, D.

    1986-07-01

    Selected examples of advanced accelerator concepts are reviewed. Such plasma accelerators as plasma beat wave accelerator, plasma wake field accelerator, and plasma grating accelerator are discussed particularly as examples of concepts for accelerating relativistic electrons or positrons. Also covered are the pulsed electron-beam, pulsed laser accelerator, inverse Cherenkov accelerator, inverse free-electron laser, switched radial-line accelerators, and two-beam accelerator. Advanced concepts for ion acceleration discussed include the electron ring accelerator, excitation of waves on intense electron beams, and two-wave combinations. (LEW)

  20. Possible error-prone repair of neoplastic transformation induced by fission-spectrum neutrons

    SciTech Connect

    Hill, C.K.; Han, A.; Elkind, M.M.

    1983-07-18

    We have examined the effect of fission-spectrum neutrons from the JANUS reactor at Argonne National Laboratory, delivered either as acute or protracted irradiation, on the incidence of neoplastic transformation in the C3H 1OT1/2 mouse embryo cell line. Acute exposures were delivered at 10 to 38 rads/min, protracted exposures at 0.086 or 0.43 rad/min. The total doses for both ranged from 2.4 to 350 rads. In the low dose region (2.4 to 80 rads), there was a large enhancement in transformation frequency when the neutrons were delivered at the low dose rates compared with the high dose rates, but the survival of the cells was not significantly different between the two exposure conditions. Analysis of the initial parts of the curves shows that the regression line for protracted doses is about 9 times steeper than that for single acute exposures. Finally, the possibility is discussed that an error-prone repair process may be causing the enhanced transformation frequency by protracted neutron exposures. 12 references, 2 figures, 1 table.

  1. Accelerators and the Accelerator Community

    SciTech Connect

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  2. Impact accelerations

    NASA Technical Reports Server (NTRS)

    Vongierke, H. E.; Brinkley, J. W.

    1975-01-01

    The degree to which impact acceleration is an important factor in space flight environments depends primarily upon the technology of capsule landing deceleration and the weight permissible for the associated hardware: parachutes or deceleration rockets, inflatable air bags, or other impact attenuation systems. The problem most specific to space medicine is the potential change of impact tolerance due to reduced bone mass and muscle strength caused by prolonged weightlessness and physical inactivity. Impact hazards, tolerance limits, and human impact tolerance related to space missions are described.

  3. Cell-Autonomous Progeroid Changes in Conditional Mouse Models for Repair Endonuclease XPG Deficiency

    PubMed Central

    Vermeij, Wilbert P.; Tresini, Maria; Weymaere, Michael; Menoni, Hervé; Brandt, Renata M. C.; de Waard, Monique C.; Botter, Sander M.; Sarker, Altaf H.; Jaspers, Nicolaas G. J.; van der Horst, Gijsbertus T. J.; Cooper, Priscilla K.; Hoeijmakers, Jan H. J.; van der Pluijm, Ingrid

    2014-01-01

    As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg−/− mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg−/− mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging. PMID:25299392

  4. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency

    SciTech Connect

    Barnhoorn, Sander; Uittenboogaard, Lieneke M.; Jaarsma, Dick; Vermeij, Wilbert P.; Tresini, Maria; Weymaere, Michael; Menoni, Hervé; Brandt, Renata M. C.; de Waard, Monique C.; Botter, Sander M.; Sarker, Altaf H.; Jaspers, Nicolaas G. J.; van der Horst, Gijsbertus T. J.; Cooper, Priscilla K.; Hoeijmakers, Jan H. J.; van der Pluijm, Ingrid; Niedernhofer, Laura J.

    2014-10-09

    As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg-/- mouse model which—in a C57BL6/FVB F1 hybrid genetic background—displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg-/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.

  5. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency

    DOE PAGES

    Barnhoorn, Sander; Uittenboogaard, Lieneke M.; Jaarsma, Dick; ...

    2014-10-09

    As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg-/- mouse model which—in a C57BL6/FVB F1 hybrid genetic background—displays manymore » progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg-/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.« less

  6. Silica-Triggered Autoimmunity in Lupus-Prone Mice Blocked by Docosahexaenoic Acid Consumption

    PubMed Central

    Bates, Melissa A.; Brandenberger, Christina; Langohr, Ingeborg I.; Kumagai, Kazuyoshi; Lock, Adam L.; Harkema, Jack R.; Holian, Andrij; Pestka, James J.

    2016-01-01

    Occupational exposure to respirable crystalline silica (cSiO2, quartz) is etiologically linked to systemic lupus erythematosus (lupus) and other human autoimmune diseases (ADs). In the female NZBWF1 mouse, a widely used animal model that is genetically prone to lupus, short-term repeated intranasal exposure to cSiO2 triggers premature initiation of autoimmune responses in the lungs and kidneys. In contrast to cSiO2’s triggering action, consumption of the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents spontaneous onset of autoimmunity in this mouse strain. The aim of this study was to test the hypothesis that consumption of DHA will prevent cSiO2-triggered autoimmunity in the female NZBWF1 mouse. Mice (6 wk old) were fed isocaloric AIN-93G diets containing 0.0, 0.4, 1.2 or 2.4% DHA. Two wk after initiating feeding, mice were intranasally instilled with 1 mg cSiO2 once per wk for 4 wk and maintained on experimental diets for an additional 12 wk. Mice were then sacrificed and the lung, blood and kidney assessed for markers of inflammation and autoimmunity. DHA was incorporated into lung, red blood cells and kidney from diet in a concentration-dependent fashion. Dietary DHA dose-dependently suppressed cSiO2-triggered perivascular leukocyte infiltration and ectopic lymphoid tissue neogenesis in the lung. DHA consumption concurrently inhibited cSiO2–driven elevation of proinflammatory cytokines, B-cell proliferation factors, IgG and anti-dsDNA Ig in both bronchoalveolar lavage fluid and plasma. DHA’s prophylactic effects were further mirrored in reduced proteinuria and glomerulonephritis in cSiO2-treated mice. Taken together, these results reveal that DHA consumption suppresses cSiO2 triggering of autoimmunity in female NZBWF1 mice as manifested in the lung, blood and kidney. Our findings provide novel insight into how dietary modulation of the lipidome might be used to prevent or delay triggering of AD by cSiO2. Such knowledge opens the

  7. Error-Prone PCR-Based Mutagenesis Strategy for Rapidly Generating High-Yield Influenza Vaccine Candidates

    PubMed Central

    Ye, Jianqiang; Wen, Feng; Xu, Yifei; Zhao, Nan; Long, Liping; Sun, Hailiang; Yang, Jialiang; Cooley, Jim; Pharr, G. Todd; Webby, Richard; Wan, Xiu-Feng

    2015-01-01

    Vaccination is the primary strategy for the prevention and control of influenza outbreaks. However, the manufacture of influenza vaccine requires a high-yield seed strain, and the conventional methods for generating such strains are time consuming. In this study, we developed a novel method to rapidly generate high-yield candidate vaccine strains by integrating error-prone PCR, site-directed mutagenesis strategies, and reverse genetics. We used this method to generate seed strains for the influenza A(H1N1)pdm09 virus and produced six high-yield candidate strains. We used a mouse model to assess the efficacy of two of the six candidate strains as a vaccine seed virus: both strains provided complete protection in mice against lethal challenge, thus validating our method. Results confirmed that the efficacy of these candidate vaccine seed strains was not affected by the yield-optimization procedure. PMID:25899178

  8. SHAME AND GUILT-PRONENESS AS MEDIATORS OF ASSOCIATIONS BETWEEN GENERAL CAUSALITY ORIENTATIONS AND DEPRESSIVE SYMPTOMS

    PubMed Central

    YOUNG, CHELSIE M.; NEIGHBORS, CLAYTON; DIBELLO, ANGELO M.; TRAYLOR, ZACHARY K.; TOMKINS, MARY

    2017-01-01

    The present study examined the roles of shame- and guilt-proneness as mediators of associations between general causality orientations and depressive symptoms. We expected autonomy would be associated with less depressive symptoms based on higher guilt-proneness and lower shame-proneness, whereas control would be associated with more depressive symptoms based on lower guilt-proneness and higher shame-proneness. Undergraduates (N = 354) completed assessments of general causality orientations, shame- and guilt-proneness, and depressive symptoms in exchange for extra credit. Results of mediation analyses were generally supportive of the framework indicating that shame- and guilt-proneness mediate associations between self-determination and depressive symptoms. Autonomy was indirectly associated with less depressive symptoms through positive associations with guilt-proneness, in spite of unexpected positive associations with shame-proneness. Control and impersonal orientation were indirectly associated with more depressive symptoms through positive associations with shame-proneness. Results extend previous research relating self-determination to mental health in providing preliminary support suggesting that individual differences in self-determination facilitate differential tendencies in experiencing guilt and shame.

  9. Jerky driving--An indicator of accident proneness?

    PubMed

    Bagdadi, Omar; Várhelyi, András

    2011-07-01

    This study uses continuously logged driving data from 166 private cars to derive the level of jerks caused by the drivers during everyday driving. The number of critical jerks found in the data is analysed and compared with the self-reported accident involvement of the drivers. The results show that the expected number of accidents for a driver increases with the number of critical jerks caused by the driver. Jerk analyses make it possible to identify safety critical driving behaviour or "accident prone" drivers. They also facilitate the development of safety measures such as active safety systems or advanced driver assistance systems, ADAS, which could be adapted for specific groups of drivers or specific risky driving behaviour.

  10. Quantitative electroencephalography as a biomarker for proneness toward developing psychosis.

    PubMed

    Fuggetta, Giorgio; Bennett, Matthew A; Duke, Philip A; Young, Andrew M J

    2014-03-01

    The fully dimensional approach to the relationship between schizotypal personality traits and schizophrenia describes schizotypy as a continuum throughout the general population ranging from low schizotypy (LoS) and psychological health to high schizotypy (HiS) and psychosis-proneness. However, no biological markers have yet been discovered that reliably quantify an individual's degree of schizotypy and/or psychosis. This study aimed to evaluate quantitative electroencephalographic (qEEG) measures of power spectra as potential biomarkers of the proneness towards the development of psychosis in schizotypal individuals. The resting-state oscillatory brain dynamics under eyes-closed condition from 16 LoS and 16 HiS individuals were analysed for qEEG measures of background rhythm frequency, relative power in δ, θ, low-α, high-α, low-β, high-β and low-γ frequency bands, and the high-temporal cross-correlation of power spectra between low- and high-frequency bands observed by averaging signals from whole-head EEG electrodes. HiS individuals at rest locked the thalamocortical loop in the low-α band at a lower-frequency oscillation and displayed an abnormally high level of neural synchronisation. In addition, the high-α band was found to be positively correlated with both the high-β and low-γ bands unlike LoS individuals, indicating widespread thalamocortical resonance in HiS individuals. The increase of regional alpha oscillations in HiS individuals suggests abnormal high-level attention, whereas the pattern of correlation between frequency bands resembles the thalamocortical dysrhythmia phenomenon which underlies the symptomatology of a variety of neuropsychiatric disorders including schizophrenia. These qEEG biomarkers may aid clinicians in identifying HiS individuals with a high-risk of developing psychosis.

  11. Augmented Computer Mouse Would Measure Applied Force

    NASA Technical Reports Server (NTRS)

    Li, Larry C. H.

    1993-01-01

    Proposed computer mouse measures force of contact applied by user. Adds another dimension to two-dimensional-position-measuring capability of conventional computer mouse; force measurement designated to represent any desired continuously variable function of time and position, such as control force, acceleration, velocity, or position along axis perpendicular to computer video display. Proposed mouse enhances sense of realism and intuition in interaction between operator and computer. Useful in such applications as three-dimensional computer graphics, computer games, and mathematical modeling of dynamics.

  12. Single Molecule Characterization of α-Synuclein in Aggregation-Prone States

    PubMed Central

    Trexler, Adam J.; Rhoades, Elizabeth

    2010-01-01

    α-Synuclein (αS) is an intrinsically disordered protein whose aggregation into ordered, fibrillar structures underlies the pathogenesis of Parkinson's disease. A full understanding of the factors that cause its conversion from soluble protein to insoluble aggregate requires characterization of the conformations of the monomer protein under conditions that favor aggregation. Here we use single molecule Förster resonance energy transfer to probe the structure of several aggregation-prone states of αS. Both low pH and charged molecules have been shown to accelerate the aggregation of αS and induce conformational changes in the protein. We find that at low pH, the C-terminus of αS undergoes substantial collapse, with minimal effect on the N-terminus and central region. The proximity of the N- and C-termini and the global dimensions of the protein are relatively unaffected by the C-terminal collapse. Moreover, although compact at low pH, with restricted chain motion, the structure of the C-terminus appears to be random. Low pH has a dramatically different effect on αS structure than the molecular aggregation inducers spermine and heparin. Binding of these molecules gives rise to only minor conformational changes in αS, suggesting that their mechanism of aggregation enhancement is fundamentally different from that of low pH. PMID:21044603

  13. Accelerator system and method of accelerating particles

    NASA Technical Reports Server (NTRS)

    Wirz, Richard E. (Inventor)

    2010-01-01

    An accelerator system and method that utilize dust as the primary mass flux for generating thrust are provided. The accelerator system can include an accelerator capable of operating in a self-neutralizing mode and having a discharge chamber and at least one ionizer capable of charging dust particles. The system can also include a dust particle feeder that is capable of introducing the dust particles into the accelerator. By applying a pulsed positive and negative charge voltage to the accelerator, the charged dust particles can be accelerated thereby generating thrust and neutralizing the accelerator system.

  14. A physical map of the mouse genome.

    PubMed

    Gregory, Simon G; Sekhon, Mandeep; Schein, Jacqueline; Zhao, Shaying; Osoegawa, Kazutoyo; Scott, Carol E; Evans, Richard S; Burridge, Paul W; Cox, Tony V; Fox, Christopher A; Hutton, Richard D; Mullenger, Ian R; Phillips, Kimbly J; Smith, James; Stalker, Jim; Threadgold, Glen J; Birney, Ewan; Wylie, Kristine; Chinwalla, Asif; Wallis, John; Hillier, LaDeana; Carter, Jason; Gaige, Tony; Jaeger, Sara; Kremitzki, Colin; Layman, Dan; Maas, Jason; McGrane, Rebecca; Mead, Kelly; Walker, Rebecca; Jones, Steven; Smith, Michael; Asano, Jennifer; Bosdet, Ian; Chan, Susanna; Chittaranjan, Suganthi; Chiu, Readman; Fjell, Chris; Fuhrmann, Dan; Girn, Noreen; Gray, Catharine; Guin, Ran; Hsiao, Letticia; Krzywinski, Martin; Kutsche, Reta; Lee, Soo Sen; Mathewson, Carrie; McLeavy, Candice; Messervier, Steve; Ness, Steven; Pandoh, Pawan; Prabhu, Anna-Liisa; Saeedi, Parvaneh; Smailus, Duane; Spence, Lorraine; Stott, Jeff; Taylor, Sheryl; Terpstra, Wesley; Tsai, Miranda; Vardy, Jill; Wye, Natasja; Yang, George; Shatsman, Sofiya; Ayodeji, Bola; Geer, Keita; Tsegaye, Getahun; Shvartsbeyn, Alla; Gebregeorgis, Elizabeth; Krol, Margaret; Russell, Daniel; Overton, Larry; Malek, Joel A; Holmes, Mike; Heaney, Michael; Shetty, Jyoti; Feldblyum, Tamara; Nierman, William C; Catanese, Joseph J; Hubbard, Tim; Waterston, Robert H; Rogers, Jane; de Jong, Pieter J; Fraser, Claire M; Marra, Marco; McPherson, John D; Bentley, David R

    2002-08-15

    A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.

  15. Ubiquinol-10 Supplementation Activates Mitochondria Functions to Decelerate Senescence in Senescence-Accelerated Mice

    PubMed Central

    Tian, Geng; Sawashita, Jinko; Kubo, Hiroshi; Nishio, Shin-ya; Hashimoto, Shigenari; Suzuki, Nobuyoshi; Yoshimura, Hidekane; Tsuruoka, Mineko; Wang, Yaoyong; Liu, Yingye; Luo, Hongming; Xu, Zhe; Mori, Masayuki; Kitano, Mitsuaki; Hosoe, Kazunori; Takeda, Toshio; Usami, Shin-ichi

    2014-01-01

    Abstract Aim: The present study was conducted to define the relationship between the anti-aging effect of ubiquinol-10 supplementation and mitochondrial activation in senescence-accelerated mouse prone 1 (SAMP1) mice. Results: Here, we report that dietary supplementation with ubiquinol-10 prevents age-related decreases in the expression of sirtuin gene family members, which results in the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a major factor that controls mitochondrial biogenesis and respiration, as well as superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), which are major mitochondrial antioxidant enzymes. Ubiquinol-10 supplementation can also increase mitochondrial complex I activity and decrease levels of oxidative stress markers, including protein carbonyls, apurinic/apyrimidinic sites, malondialdehydes, and increase the reduced glutathione/oxidized glutathione ratio. Furthermore, ubiquinol-10 may activate Sirt1 and PGC-1α by increasing cyclic adenosine monophosphate (cAMP) levels that, in turn, activate cAMP response element-binding protein (CREB) and AMP-activated protein kinase (AMPK). Innovation and Conclusion: These results show that ubiquinol-10 may enhance mitochondrial activity by increasing levels of SIRT1, PGC-1α, and SIRT3 that slow the rate of age-related hearing loss and protect against the progression of aging and symptoms of age-related diseases. Antioxid. Redox Signal. 20, 2606–2620 PMID:24124769

  16. Neuroprotective role of intermittent fasting in senescence-accelerated mice P8 (SAMP8).

    PubMed

    Tajes, M; Gutierrez-Cuesta, J; Folch, J; Ortuño-Sahagun, D; Verdaguer, E; Jiménez, A; Junyent, F; Lau, A; Camins, A; Pallàs, M

    2010-09-01

    Dietary interventions have been proposed as a way to increase lifespan and improve health. The senescence-accelerated prone 8 (SAMP8) mice have a shorter lifespan and show alterations in the central nervous system. Moreover, this mouse strain shows decreased sirtuin 1 protein expression and elevated expression of the acetylated targets NFkappaB and FoxO1, which are implicated in transcriptional control of key genes in cell proliferation and cell survival, in reference to control strain, SAMR1. After eight weeks of intermittent fasting, sirtuin 1 protein expression was recovered in SAMP8. This recovery was accompanied by a reduction in the two acetylated targets. Furthermore, SAMP8 showed a lower protein expression of BDNF and HSP70 while intermittent fasting re-established normal values. The activation of JNK and FoxO1 was also reduced in SAMP8 mice subjected to an IF regimen, compared with control SAMP8. Our findings provide new insights into the participation of sirtuin 1 in ageing and point to a potential novel application of this enzyme to prevent frailty due to ageing processes in the brain.

  17. Procrastination and suicide proneness: A moderated-mediation model for cognitive schemas and gender.

    PubMed

    Klibert, Jeffrey; LeLeux-LaBarge, Kayla; Tarantino, Nicholas; Yancey, Thresa; Lamis, Dorian A

    2016-07-01

    This study examined the direct and indirect paths between procrastination and suicide proneness while considering gender differences. Participants included 547 undergraduates from a southeastern university. Procrastination was positively related to suicide proneness for both genders, although this relation was stronger for women. Moderated-mediation analyses with bootstrapping highlighted insufficient self-control schemas as a mediator in the relation between procrastination and suicide proneness. However, indirect pathways did not vary by gender. Results represent an extension of the Procrastination-Health Model by highlighting the contribution of cognitive factors in explaining the relation between procrastination and suicide proneness.

  18. Acceleration modules in linear induction accelerators

    NASA Astrophysics Data System (ADS)

    Wang, Shao-Heng; Deng, Jian-Jun

    2014-05-01

    The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

  19. Multidisciplinary approach to converting power chair into motorized prone cart.

    PubMed

    Brose, Steven W; Wali, Eisha

    2014-01-01

    Pressure ulcers remain a major source of morbidity and mortality in veterans with neurologic impairment. Management of pressure ulcers typically involves pressure relief over skin regions containing wounds, but this can lead to loss of mobility and independence when the wounds are located in regions that receive pressure from sitting. An innovative, low-cost, multidisciplinary effort was undertaken to maximize quality of life in a veteran with a thoracic-4 level complete spinal cord injury and a stage 4 ischial wound. The person's power wheelchair was converted into a motorized prone cart, allowing navigation of the Department of Veterans Affairs spinal cord injury hospital ward and improved socialization while relieving pressure on the wound. Physical and occupational therapy assisted with the reconfiguration of the power chair and verified safe transfers into the chair and driving of the device. Psychology verified positive psychosocial benefit, while nursing and physician services verified an absence of unwanted pain or skin injury resulting from use of the device. Further investigation of ways to apply this technique is warranted to improve the quality of life of persons with pressure ulcers.

  20. Arthroscopic subtalar arthrodesis: the posterior approach in the prone position.

    PubMed

    Carro, Luis Perez; Golanó, Pau; Vega, Jordi

    2007-04-01

    Arthroscopic subtalar arthrodesis, as reported by Tasto, is done in the lateral decubitus position, and the portal sites are lateral. This report describes a new alternative method in which the patient is in the prone position and a posterior 2-portal approach is used, as described by van Dijk et al. The initial debridement and synovectomy are performed with 4- and 5-mm resectors. Debridement and decortication are done posterior to the interosseous ligament because only the posterior facet is fused. Denudation of the articular surfaces is performed with curettes, as well as 4.5- and 5.5-mm burs, to remove 2 mm of subchondral bone. Stabilization in 5 degrees of hindfoot valgus is accomplished with 2 percutaneous cannulated headless screws from the non-weight-bearing portion of the calcaneal tuberosity directed to a point 5 to 10 mm posterior to the anterior margin of the posterior facet. The advantages of this alternative treatment are better intra-articular visualization, more thorough preparation of the fusion site, and minimal bone removal of the lateral side with better control of the arthrodesis position and with less chance of malunion, as well as the possibility to perform a concomitant surgical fusion or debridement of the ankle joint during the same operative procedure with no need for additional portals or orientation.

  1. Development of Korean Smartphone Addiction Proneness Scale for Youth

    PubMed Central

    Kim, Dongil; Lee, Yunhee; Lee, Juyoung; Nam, JeeEun Karin; Chung, Yeoju

    2014-01-01

    This study developed a Smartphone Addiction Proneness Scale (SAPS) based on the existing internet and cellular phone addiction scales. For the development of this scale, 29 items (1.5 times the final number of items) were initially selected as preliminary items, based on the previous studies on internet/phone addiction as well as the clinical experience of involved experts. The preliminary scale was administered to a nationally representative sample of 795 students in elementary, middle, and high schools across South Korea. Then, final 15 items were selected according to the reliability test results. The final scale consisted of four subdomains: (1) disturbance of adaptive functions, (2) virtual life orientation, (3) withdrawal, and (4) tolerance. The final scale indicated a high reliability with Cronbach's α of .880. Support for the scale's criterion validity has been demonstrated by its relationship to the internet addiction scale, KS-II (r  =  .49). For the analysis of construct validity, we tested the Structural Equation Model. The results showed the four-factor structure to be valid (NFI  =  .943, TLI  =  .902, CFI  =  .902, RMSEA  =  .034). Smartphone addiction is gaining a greater spotlight as possibly a new form of addiction along with internet addiction. The SAPS appears to be a reliable and valid diagnostic scale for screening adolescents who may be at risk of smartphone addiction. Further implications and limitations are discussed. PMID:24848006

  2. Signature of an aggregation-prone conformation of tau

    NASA Astrophysics Data System (ADS)

    Eschmann, Neil A.; Georgieva, Elka R.; Ganguly, Pritam; Borbat, Peter P.; Rappaport, Maxime D.; Akdogan, Yasar; Freed, Jack H.; Shea, Joan-Emma; Han, Songi

    2017-03-01

    The self-assembly of the microtubule associated tau protein into fibrillar cell inclusions is linked to a number of devastating neurodegenerative disorders collectively known as tauopathies. The mechanism by which tau self-assembles into pathological entities is a matter of much debate, largely due to the lack of direct experimental insights into the earliest stages of aggregation. We present pulsed double electron-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6*, in transient as aggregation happens. By monitoring the end-to-end distance distribution of these segments as a function of aggregation time, we show that the PHF6(*) regions dramatically extend to distances commensurate with extended β-strand structures within the earliest stages of aggregation, well before fibril formation. Combined with simulations, our experiments show that the extended β-strand conformational state of PHF6(*) is readily populated under aggregating conditions, constituting a defining signature of aggregation-prone tau, and as such, a possible target for therapeutic interventions.

  3. Development of Korean Smartphone addiction proneness scale for youth.

    PubMed

    Kim, Dongil; Lee, Yunhee; Lee, Juyoung; Nam, JeeEun Karin; Chung, Yeoju

    2014-01-01

    This study developed a Smartphone Addiction Proneness Scale (SAPS) based on the existing internet and cellular phone addiction scales. For the development of this scale, 29 items (1.5 times the final number of items) were initially selected as preliminary items, based on the previous studies on internet/phone addiction as well as the clinical experience of involved experts. The preliminary scale was administered to a nationally representative sample of 795 students in elementary, middle, and high schools across South Korea. Then, final 15 items were selected according to the reliability test results. The final scale consisted of four subdomains: (1) disturbance of adaptive functions, (2) virtual life orientation, (3) withdrawal, and (4) tolerance. The final scale indicated a high reliability with Cronbach's α of .880. Support for the scale's criterion validity has been demonstrated by its relationship to the internet addiction scale, KS-II (r  =  .49). For the analysis of construct validity, we tested the Structural Equation Model. The results showed the four-factor structure to be valid (NFI  =  .943, TLI  =  .902, CFI  =  .902, RMSEA  =  .034). Smartphone addiction is gaining a greater spotlight as possibly a new form of addiction along with internet addiction. The SAPS appears to be a reliable and valid diagnostic scale for screening adolescents who may be at risk of smartphone addiction. Further implications and limitations are discussed.

  4. Signature of an aggregation-prone conformation of tau

    PubMed Central

    Eschmann, Neil A.; Georgieva, Elka R.; Ganguly, Pritam; Borbat, Peter P.; Rappaport, Maxime D.; Akdogan, Yasar; Freed, Jack H.; Shea, Joan-Emma; Han, Songi

    2017-01-01

    The self-assembly of the microtubule associated tau protein into fibrillar cell inclusions is linked to a number of devastating neurodegenerative disorders collectively known as tauopathies. The mechanism by which tau self-assembles into pathological entities is a matter of much debate, largely due to the lack of direct experimental insights into the earliest stages of aggregation. We present pulsed double electron-electron resonance measurements of two key fibril-forming regions of tau, PHF6 and PHF6*, in transient as aggregation happens. By monitoring the end-to-end distance distribution of these segments as a function of aggregation time, we show that the PHF6(*) regions dramatically extend to distances commensurate with extended β-strand structures within the earliest stages of aggregation, well before fibril formation. Combined with simulations, our experiments show that the extended β-strand conformational state of PHF6(*) is readily populated under aggregating conditions, constituting a defining signature of aggregation-prone tau, and as such, a possible target for therapeutic interventions. PMID:28303942

  5. Progress on plasma accelerators

    SciTech Connect

    Chen, P.

    1986-05-01

    Several plasma accelerator concepts are reviewed, with emphasis on the Plasma Beat Wave Accelerator (PBWA) and the Plasma Wake Field Accelerator (PWFA). Various accelerator physics issues regarding these schemes are discussed, and numerical examples on laboratory scale experiments are given. The efficiency of plasma accelerators is then revealed with suggestions on improvements. Sources that cause emittance growth are discussed briefly.

  6. 44 CFR 60.22 - Planning considerations for flood-prone areas.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... flood-prone areas. 60.22 Section 60.22 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing Flood-Prone, Mudslide...

  7. 44 CFR 60.22 - Planning considerations for flood-prone areas.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... flood-prone areas. 60.22 Section 60.22 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing Flood-Prone, Mudslide...

  8. 44 CFR 60.22 - Planning considerations for flood-prone areas.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... flood-prone areas. 60.22 Section 60.22 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing Flood-Prone, Mudslide...

  9. 44 CFR 60.22 - Planning considerations for flood-prone areas.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... flood-prone areas. 60.22 Section 60.22 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing Flood-Prone, Mudslide...

  10. Critical Differences between the Type-A Prone and Type-A Personalitites.

    ERIC Educational Resources Information Center

    Cassel, Russell N.; Cassel, Susie L.

    1984-01-01

    Type-A Prone and Type-A personalities were assessed on the basis of the Cassel Type-A Personality Assessment Profile. Statistical data analysis indicated differences in positive lifestyle, blood pressure, and self-control and no differences in negative lifestyle, pulse rate, or peripheral temperature. Type-A Prone and Type-A norm profiles were…

  11. Suicide Proneness in College Students: Relationships with Gender, Procrastination, and Achievement Motivation

    ERIC Educational Resources Information Center

    Klibert, Jeffrey; Langhinrichsen-Rohling, Jennifer; Luna, Amy; Robichaux, Michelle

    2011-01-01

    This study examined the relationships between 2 academic dispositions (i.e., procrastination and achievement motivation) and 2 indices of suicidal proneness in college women and men. The degree these 2 academic dispositions could predict unique variance in suicide proneness scores, above and beyond the influence of depression and self-esteem was…

  12. 44 CFR 60.23 - Planning considerations for mudslide (i.e., mudflow)-prone areas.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., Mudslide (i.e., Mudflow)-Prone and Flood-Related Erosion-Prone Areas § 60.23 Planning considerations for... location of public utilities and service facilities, such as sewer, water, gas and electrical systems and..., flood plain, mudslide (i.e., mudflow), soil, land, and water regulation in neighboring communities;...

  13. The Relationship of Stress Arousal and Stress Prone Personality Traits to Menstrual Distress.

    ERIC Educational Resources Information Center

    Marini, David C.

    The various relationships of stress arousal and stress-prone personality traits to menstrual distress were investigated in order to quantify psychophysiological arousal differences between high and low menstrual distress symptom reporters and examine differences in stress-prone personality traits between high and low menstrual distress symptom…

  14. Preliminary Results on Setup Precision of Prone-Lateral Patient Positioning for Whole Breast Irradiation

    SciTech Connect

    Veldeman, Liv; Speleers, Bruno; Bakker, Marlies; Jacobs, Filip; Coghe, Marc; De Gersem, Werner; Impens, Aline; Nechelput, Sarah; De Wagter, Carlos

    2010-09-01

    Purpose: The aim of this study was to develop a rapid and reproducible technique for prone positioning and to compare dose-volume indices in prone and supine positions. Methods and Materials: Eighteen patients underwent computed tomography imaging for radiotherapy planning in prone and supine position. Experience was gained in the first eight patients, which lead to modifications of the Horizon prone breast board (Civco Medical Solutions, Orange City, Iowa, USA) and the patient setup technique. A unilateral breast holder (U-BH) was developed (Van de Velde, Schellebelle, Belgium) to retract the contralateral breast away from the treated breast. The technique was then applied to an additional 10 patients. The setup precision was evaluated using daily cone-beam CT. Results: Modifications to the breast board were made to secure a prone-lateral rather then a pure prone position. We evolved from a classical setup using laser marks on the patients' body to a direct breast setup using marks on the breast only. The setup precision of the direct positioning procedure with the modified breast board and the U-BH is comparable to supine setup data in the literature. Dose-volume indices for heart and lung show significantly better results for prone than for supine position, and dose homogeneity within the treated breast did not differ according to the treatment position. Conclusions: The setup precision of our prone-lateral positioning technique is comparable to supine data in literature. Our data show the advantage of prone radiotherapy to spare the lung and heart. Further research is necessary to reduce the duration of prone setup.

  15. Lifespan and reproduction in brain-specific miR-29-knockdown mouse.

    PubMed

    Takeda, Toru; Tanabe, Hiroyuki

    2016-03-18

    The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post-reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR-29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction.

  16. Modeling fluxes and form in landslide-prone terrain

    NASA Astrophysics Data System (ADS)

    Roering, J. J.; Booth, A. M.; Stock, J. D.

    2011-12-01

    Landslides dramatically alter the Earth's surface over short timescales. The mass transfer associated with a limited number of slope failures can dominate the sediment budget of a region for decades or longer. The initiation, failure geometry, and runout of individual landslides depend on a range of factors and cannot be predicted from current models. Given these realities of landslide behavior over human timescales, it is challenging to reasonably represent these processes in landscape evolution models. Here, we evaluate the ability of two landslide models, both of which are formulated to apply at geomorphic timescales, to generate topographic patterns and sediment flux rates observed in natural landscapes. Episodic debris flow activity is ubiquitous in steep, low-order mountainous catchments and generates valley networks with low concavity. A physically-based model for debris flow incision (Stock and Dietrich, GSA Bull, 2006) proposes that incision rates depend on the frequency, volume, and velocity of debris flows as well as the density of trigger sites and the state of bedrock weathering in low-order valleys. Valley slope angles are predicted to decline with drainage area according to how these properties vary spatially. We calibrated the model for a well-studied small catchment in the Oregon Coast Range using cosmogenic radionuclide erosion rates and then analyzed the slope-area signature of low-order valleys across much of the Central Oregon Coast Range to explore spatial variations in baselevel lowering. This endeavor shows that baselevel lowering rates vary significantly due to patches of resistant bedrock, drainage reorganization, and tectonic forcing. In regions with weak sedimentary bedrock, earthflows can reduce hillslope gradients, promote gullying, and dominate sediment yield through their downslope translation. A one-dimensional, physically-based model for earthflow-prone hillslope evolution (Booth and Roering, JGR, in press) incorporates earthflow

  17. Nobiletin, a citrus flavonoid, improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of Alzheimer's disease (3XTg-AD).

    PubMed

    Nakajima, Akira; Aoyama, Yuki; Shin, Eun-Joo; Nam, Yunsung; Kim, Hyoung-Chun; Nagai, Taku; Yokosuka, Akihito; Mimaki, Yoshihiro; Yokoi, Tsuyoshi; Ohizumi, Yasushi; Yamada, Kiyofumi

    2015-08-01

    Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function. Increasing evidence indicates that the production and accumulation of amyloid β (Aβ), particularly soluble Aβ oligomers, is central to the pathogenesis of AD. Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairment in olfactory-bulbectomized mice, amyloid precursor protein transgenic mice, NMDA receptor antagonist-treated mice, and senescence-accelerated mouse prone 8. Here, we present evidence that this natural compound improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of AD (3XTg-AD) that progressively develops amyloid plaques, neurofibrillary tangles, and cognitive impairments. Treatment with nobiletin (30 mg/kg) for 3 months reversed the impairment of short-term memory and recognition memory in 3XTg-AD mice. Our ELISA analysis also showed that nobiletin reduced the levels of soluble Aβ1-40 in the brain of 3XTg-AD mice. Furthermore, nobiletin reduced ROS levels in the hippocampus of 3XTg-AD as well as wild-type mice. These results suggest that this natural compound has potential to become a novel drug for the treatment and prevention of AD.

  18. Electroacupuncture Treatment Improves Learning-Memory Ability and Brain Glucose Metabolism in a Mouse Model of Alzheimer's Disease: Using Morris Water Maze and Micro-PET

    PubMed Central

    Jiang, Jing; Gao, Kai; Zhou, Yuan; Xu, Anping; Shi, Suhua; Liu, Gang; Li, Zhigang

    2015-01-01

    Introduction. Alzheimer's disease (AD) causes progressive hippocampus dysfunctions leading to the impairment of learning and memory ability and low level of uptake rate of glucose in hippocampus. What is more, there is no effective treatment for AD. In this study, we evaluated the beneficial and protective effects of electroacupuncture in senescence-accelerated mouse prone 8 (SAMP8). Method. In the electroacupuncture paradigm, electroacupuncture treatment was performed once a day for 15 days on 7.5-month-old SAMP8 male mice. In the normal control paradigm and AD control group, 7.5-month-old SAMR1 male mice and SAMP8 male mice were grabbed and bandaged while electroacupuncture group therapy, in order to ensure the same treatment conditions, once a day, 15 days. Results. From the Morris water maze (MWM) test, we found that the treatment of electroacupuncture can improve the spatial learning and memory ability of SAMP8 mouse, and from the micro-PET test, we proved that after the electroacupuncture treatment the level of uptake rate of glucose in hippocampus was higher than normal control group. Conclusion. These results suggest that the treatment of electroacupuncture may provide a viable treatment option for AD. PMID:25821477

  19. Is decreased diameter of renal pelvis in prone position an indicator of successful pyeloplasty?

    PubMed Central

    Sharma, Gyanendra; Sharma, Anshu; Leung, Vivian Yee-Fong; Chu, Winnie Chiu-Wing

    2016-01-01

    Objective: To evaluate patients who had undergone pyeloplasty for pelviureteric junction obstruction, by measuring the anteroposterior diameter (APD) of the renal pelvis in supine and prone positions, and determine whether a decrease in APD in prone position can exclude obstruction in dilated renal system. Materials and Methods: From January 2012 to December 2013, patients who had undergone pyeloplasty were evaluated by ultrasound in two centers. The difference of APD of the renal pelvis in supine and prone positions was obtained. Correlation was made with the pre- and post-pyeloplasty renal function by radionuclide renogram. Results: There were 42 patients (31 males, 11 females; age range 5 months to 18 years). Residual hydronephrosis was detected in 41 patients of whom 35 patients (85%) showed decrease in APD by >10% in prone position. These patients and the one without hydronephrosis showed either no deterioration or improvement in renal function. Six patients (15%) showed either no change or increase in APD in prone position. Three patients (7.5%) were confirmed to have decrease in renal function indicating obstruction. Three patients (7.5%) showed no deterioration of renal function, but sluggish drainage on radionuclide renogram. Conclusion: Demonstration of decreased APD of renal pelvis in prone position by ultrasound is useful to differentiate obstructed from non-obstructed dilated renal system, and it correctly identified 85% candidates with successful pyeloplasty. In patients with no decrease or increase in APD at prone position, further follow-up is recommended to rule out obstruction. PMID:27081219

  20. Regional ventilation-perfusion distribution is more uniform in the prone position

    NASA Technical Reports Server (NTRS)

    Mure, M.; Domino, K. B.; Lindahl, S. G.; Hlastala, M. P.; Altemeier, W. A.; Glenny, R. W.

    2000-01-01

    The arterial blood PO(2) is increased in the prone position in animals and humans because of an improvement in ventilation (VA) and perfusion (Q) matching. However, the mechanism of improved VA/Q is unknown. This experiment measured regional VA/Q heterogeneity and the correlation between VA and Q in supine and prone positions in pigs. Eight ketamine-diazepam-anesthetized, mechanically ventilated pigs were studied in supine and prone positions in random order. Regional VA and Q were measured using fluorescent-labeled aerosols and radioactive-labeled microspheres, respectively. The lungs were dried at total lung capacity and cubed into 603-967 small ( approximately 1.7-cm(3)) pieces. In the prone position the homogeneity of the ventilation distribution increased (P = 0.030) and the correlation between VA and Q increased (correlation coefficient = 0.72 +/- 0.08 and 0.82 +/- 0.06 in supine and prone positions, respectively, P = 0.03). The homogeneity of the VA/Q distribution increased in the prone position (P = 0.028). We conclude that the improvement in VA/Q matching in the prone position is secondary to increased homogeneity of the VA distribution and increased correlation of regional VA and Q.

  1. Future accelerator technology

    SciTech Connect

    Sessler, A.M.

    1986-05-01

    A general discussion is presented of the acceleration of particles. Upon this foundation is built a categorization scheme into which all accelerators can be placed. Special attention is devoted to accelerators which employ a wake-field mechanism and a restricting theorem is examined. It is shown how the theorem may be circumvented. Comments are made on various acceleration schemes.

  2. ACCELERATION AND THE GIFTED.

    ERIC Educational Resources Information Center

    GIBSON, ARTHUR R.; STEPHANS, THOMAS M.

    ACCELERATION OF PUPILS AND SUBJECTS IS CONSIDERED A MEANS OF EDUCATING THE ACADEMICALLY GIFTED STUDENT. FIVE INTRODUCTORY ARTICLES PROVIDE A FRAMEWORK FOR THINKING ABOUT ACCELERATION. FIVE PROJECT REPORTS OF ACCELERATED PROGRAMS IN OHIO ARE INCLUDED. ACCELERATION IS NOW BEING REGARDED MORE FAVORABLY THAN FORMERLY, BECAUSE METHODS HAVE BEEN…

  3. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2005-06-14

    A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

  4. Laser driven ion accelerator

    DOEpatents

    Tajima, Toshiki

    2006-04-18

    A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

  5. Individual Differences in Emotion Regulation, Childhood Trauma and Proneness to Shame and Guilt in Adolescence

    PubMed Central

    2016-01-01

    Dispositional shame and guilt have been associated with psychopathology and an increasing number of studies have traced this relation back to adolescence. This developmental period is thought to be characterized by maturational changes in emotion regulation, which also play an important role in vulnerability to psychopathology, but little is known about the links between emotion regulation and dispositional shame and guilt. The current study investigated the relations between individual differences in the habitual use of a wide range of emotion regulation strategies and proneness to shame and guilt in a large sample of adolescents (N = 706), aged 13 to 17 years. History of childhood trauma was also assessed. Our results showed that emotion regulation independently explained about 20% of the variance of shame-proneness and guilt-proneness. Higher use of maladaptive (e.g., Self-Blaming, Catastrophizing) and lower use of adaptive (e.g., Refocus on Planning, Positive Reappraisal) emotion regulation strategies were positively associated with shame-proneness. In contrast, lower use of maladaptive (e.g., Catastrophizing, Blaming Others) and higher use of adaptive (e.g., Refocus on Planning, Positive Reappraisal) emotion regulation strategies were associated with guilt-proneness, independent of the influence of childhood trauma, which also explained a relatively minor portion of guilt-proneness. Although there were age differences (i.e., rumination was used more by older adolescents, and the influence of emotion regulation on depression and anxiety symptoms increased with age) and sex differences (i.e., girls reported higher use of Putting into Perspective and Other Blaming compared to boys) in emotion regulation, age and sex were not significantly associated with proneness to shame and guilt. The positive relations with maladaptive emotion regulation underscores the dysfunctional nature of shame-proneness. Future studies could use longitudinal measures to establish that

  6. Prone cross-table lateral view: an alternative to the invertogram in imperforate anus

    SciTech Connect

    Narasimharao, K.L.; Prasad, G.R.; Katariya, S.; Yadav, K.; Mitra, S.K.; Pathak, I.C.

    1983-02-01

    The prone cross-table lateral radiograph provides equal or sometimes better information, compared to the invertogram, for demonstration of the level of rectal atresia in neonates. Easy positioning, better cooperation of the patient, elimination of the effect of gravity, and better delineation of the rectal gas shadow are the advantages of the prone lateral view. Among the 45 cases compared, equal findings were noted in 37, but in eight babies the level of rectal atresia was more caudal in the prone radiograph than in the invertogram.

  7. Prone-position thoracoscopic resection of posterior mediastinal lymph node metastasis from rectal cancer.

    PubMed

    Shirakawa, Yasuhiro; Noma, Kazuhiro; Koujima, Takeshi; Maeda, Naoaki; Tanabe, Shunsuke; Ohara, Toshiaki; Fujiwara, Toshiyoshi

    2015-02-12

    Mediastinal lymph node metastasis from colorectal cancer is rare, and barely any reports have described resection of this pathology. We report herein a successful thoracoscopic resection of mediastinal lymph node metastasis in a prone position. A 65-year-old man presented with posterior mediastinal lymph node metastasis after resection of the primary rectal cancer and metachronous hepatic metastasis. Metastatic lymph nodes were resected completely using thoracoscopic surgery in the prone position, which provided advantages of minimal invasiveness, good surgical field, and reduced ergonomic burden on the surgeon. Thoracoscopic resection in the prone position was thought to have the potential to become the standard procedure of posterior mediastinal tumors.

  8. Changes in nerve-mediated contractility of the lower urinary tract in a mouse model of premature ageing

    PubMed Central

    Triguero, D; Lafuente-Sanchis, A; Garcia-Pascual, A

    2014-01-01

    Background and Purpose A high incidence of lower urinary tract disorders is associated with ageing. In the senescent-accelerated prone (SAMP8) mouse strain and the senescent-accelerated resistant (SAMR1) strain, we compared smooth muscle contractility in responses to intrinsic neurotransmitters, both in the bladder and urethra. Experimental Approach We analysed micturition frequency, the changes in muscle tension induced by electrical field stimulation or agonist administration, the density of nerves (adrenergic, cholinergic and nitrergic) and interstitial cells (ICs), as well as cGMP accumulation in bladder and urethral preparations. Key Results Senescent mice of the SAMP8 strain displayed increased micturition frequency and excitatory contractility of neurogenic origin in the bladder. While cholinergic nerve density remained unchanged, there was a mild sensitization to ACh in male mice. Potentiation in the detrusor may be also provoked by the stronger contribution of ATP, together with reduced adrenergic innervation in males and COX-derived prostanoid production in females. The greater excitatory contractility in the urethra was probably due to the sensitization to noradrenaline, in conjunction with attenuated nitrergic relaxation. There were also fewer neuronal NOS immunoreactive (ir) nerves and vimentin-positive ICs, although the sildenafil-and diethylamine-NONOate-induced relaxations and cGMP-ir remained unchanged. Conclusions and Implications Premature senescent mice exhibit bladder and urethral hyperexcitability, coupled with reduced urethral relaxation of neurogenic origin, which could model the impaired urinary function in elderly humans. We propose that senescence-accelerated mice provide a useful tool to analyse the basic mechanisms of age-related changes in bladder and urethral function. PMID:24372152

  9. SU-E-T-307: Dosimetric Comparison of Prone Versus Supine Positioning for Adjuvant Breast Radiation Therapy

    SciTech Connect

    Pope, C; O’Connor, B; Hayes, L; Rella, J; Ruiz, B; Yang, J

    2015-06-15

    Purpose: The prone treatment position has been used to reduce ipsilateral lung and heart dose in left breast radiation. We conducted a retrospective study to evaluate the difference in the dosimetry between prone and supine treatment positions. Methods: Eight left breast cancer patients were simulated in both the supine and prone positions as a pretreatment evaluation for the optimal treatment position. Treatment plans were created for all patients in both the supine and prone positions using a field in field three dimensional planning technique. Prescribed dose was 45 Gy delivered by two tangential photon fields. Irradiated volume (IV) was evaluated by V50, V100, and dose to lung and heart by V5, V10, V20, and the mean dose were evaluated. Results: All dosimetry metrics for both the supine and prone plans met our internal normal structure guidelines which are based on Quantec data. The average IVs (50% and 100%) were 2223cc and 1361cc prone, 2315cc and 1315cc supine. The average ipsilateral lung Mean dose (0.83Gy prone vs 5.8Gy supine), V5 (1.6% prone vs 20.9% supine), V10 (0.78% prone vs 15% supine) and V20 (0.36% prone vs 11% supine) were significantly lower in prone position. Heart Mean dose (1.4Gy prone vs 2.9Gy supine), V10 (1.4% prone vs 5.0% supine) and V20 (0.4% prone vs 3.5% supine) were found improved for all patients except one where the mean dose was the same and all other values were improved. Conclusion: The prone position offer preferable dosimetry for all patients planned in our study. These patients were chosen based on the physician’s belief that they would benefit from prone treatment either because they had large pendulous breasts or due to the amount of heart seen in the field on CT simulation.

  10. Enzyme-treated Asparagus officinalis extract shows neuroprotective effects and attenuates cognitive impairment in senescence-accelerated mice.

    PubMed

    Sakurai, Takuya; Ito, Tomohiro; Wakame, Koji; Kitadate, Kentaro; Arai, Takashi; Ogasawara, Junetsu; Kizaki, Takako; Sato, Shogo; Ishibashi, Yoshinaga; Fujiwara, Tomonori; Akagawa, Kimio; Ishida, Hitoshi; Ohno, Hideki

    2014-01-01

    Increases in the number of patients with dementia involving Alzheimer's disease (AD) are seen as a grave public health problem. In neurodegenerative disorders involving AD, biological stresses, such as oxidative and inflammatory stress, induce neural cell damage. Asparagus (Asparagus officinalis) is a popular vegetable, and an extract prepared from this reportedly possesses various beneficial biological activities. In the present study, we investigated the effects of enzyme-treated asparagus extract (ETAS) on neuronal cells and early cognitive impairment of senescence-accelerated mouse prone 8 (SAMP8) mice. The expression of mRNAs for factors that exert cytoprotective and anti-apoptotic functions, such as heat-shock protein 70 and heme oxygenase-1, was upregulated in NG108-15 neuronal cells by treatment with ETAS. Moreover, when release of lactate dehydrogenase from damaged NG108-15 cells was increased for cells cultured in medium containing either the nitric oxide donor sodium nitroprusside or the hypoxia mimic reagent cobalt chloride, ETAS significantly attenuated this cell damage. Also, when contextual fear memory, which is considered to be a hippocampus-dependent memory, was significantly impaired in SAMP8 mice, ETAS attenuated the cognitive impairment. These results suggest that ETAS produces cytoprotective effects in neuronal cells and attenuates the effects on the cognitive impairment of SAMP8 mice.

  11. Accelerated progression of chronic lymphocytic leukemia in Eμ-TCL1 mice expressing catalytically inactive RAG1.

    PubMed

    Nganga, Vincent K; Palmer, Victoria L; Naushad, Hina; Kassmeier, Michele D; Anderson, Dirk K; Perry, Greg A; Schabla, Nathan M; Swanson, Patrick C

    2013-05-09

    Chronic lymphocytic leukemia (CLL) is a prevalent B-cell neoplasia that is often preceded by a more benign monoclonal CD5(+) B-cell lymphocytosis. We previously generated transgenic mice expressing catalytically inactive RAG1 (dominant-negative recombination activating gene 1 [dnRAG1] mice) that develop an early-onset indolent CD5(+) B-cell lymphocytosis attributed to a defect in secondary V(D)J rearrangements initiated to edit autoreactive B-cell receptor (BCR) specificity. Hypothesizing that CD5(+) B cells in these animals represent potential CLL precursors, we crossed dnRAG1 mice with CLL-prone Eμ-TCL1 mice to determine whether dnRAG1 expression in Eμ-TCL1 mice accelerates CLL onset. Consistent with this hypothesis, CD5(+) B-cell expansion and CLL progression occurred more rapidly in double-transgenic mice compared with Eμ-TCL1 mice. Nevertheless, CD5(+) B cells in the 2 mouse strains exhibited close similarities in phenotype, immunoglobulin gene usage, and mutation status, and expression of genes associated with immune tolerance and BCR signaling. Gene expression profiling further revealed a potential role for prolactin signaling in regulating BCR editing. These results suggest a model in which benign accumulation of CD5(+) B cells can be initiated through a failure to successfully edit autoreactive BCR specificity and may, in turn, progress to CLL upon introduction of additional genetic mutations.

  12. Accelerated progression of chronic lymphocytic leukemia in Eμ-TCL1 mice expressing catalytically inactive RAG1

    PubMed Central

    Nganga, Vincent K.; Palmer, Victoria L.; Naushad, Hina; Kassmeier, Michele D.; Anderson, Dirk K.; Perry, Greg A.; Schabla, Nathan M.

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is a prevalent B-cell neoplasia that is often preceded by a more benign monoclonal CD5+ B-cell lymphocytosis. We previously generated transgenic mice expressing catalytically inactive RAG1 (dominant-negative recombination activating gene 1 [dnRAG1] mice) that develop an early-onset indolent CD5+ B-cell lymphocytosis attributed to a defect in secondary V(D)J rearrangements initiated to edit autoreactive B-cell receptor (BCR) specificity. Hypothesizing that CD5+ B cells in these animals represent potential CLL precursors, we crossed dnRAG1 mice with CLL-prone Eμ-TCL1 mice to determine whether dnRAG1 expression in Eμ-TCL1 mice accelerates CLL onset. Consistent with this hypothesis, CD5+ B-cell expansion and CLL progression occurred more rapidly in double-transgenic mice compared with Eμ-TCL1 mice. Nevertheless, CD5+ B cells in the 2 mouse strains exhibited close similarities in phenotype, immunoglobulin gene usage, and mutation status, and expression of genes associated with immune tolerance and BCR signaling. Gene expression profiling further revealed a potential role for prolactin signaling in regulating BCR editing. These results suggest a model in which benign accumulation of CD5+ B cells can be initiated through a failure to successfully edit autoreactive BCR specificity and may, in turn, progress to CLL upon introduction of additional genetic mutations. PMID:23502221

  13. [Prone position: effect on gas exchange and functional capacity for exercise in patients with pulmonary hypertension].

    PubMed

    Bastidas-L, Andrea Carolina; Colina-Chourio, José A; Guevara, Jesnel M; Nunez, Alexis

    2015-03-01

    The objective of this investigation was to evaluate gas exchange and cardiopulmonary functional behavior in patients with pulmonary hypertension (PH) before, during and after the change to a prone position. Thirty patients with PH and alterations in gas exchange were included in the study. Gas exchange measurements were performed in four stages: at the baseline supine position and after 30, 120 and 240 minutes in prone position. Also, the patients were evaluated by the six minutes walking test (6MWT) after 30 days in prone position during night's sleep. After four hours in prone position, all patients showed an increase of PaO2 and arterial saturation of oxygen (SaO2), with a decrease of intrapulmonary shunts, improving the gas exchange and therefore the physiological demand imposed by exercise in patients with PH.

  14. Modeling interactions betweenspotted owl and barred owl populations in fire-prone forests

    EPA Science Inventory

    Background / Question / Methods Efforts to conserve northern spotted owls (Strix occidentalis caurina) in the eastern Cascades of Washington must merge the challenges of providing sufficient structurally complex forest habitat in a fire-prone landscape with the limitations impos...

  15. Smokers May Be Prone to Risks from Breast Cancer Radiation Therapy

    MedlinePlus

    ... html Smokers May Be Prone to Risks From Breast Cancer Radiation Therapy Long-term chances of heart attack, ... 29, 2017 WEDNESDAY, March 29, 2017 (HealthDay News) -- Breast cancer patients who smoke have an increased risk for ...

  16. When feeling bad leads to feeling good: guilt-proneness and affective organizational commitment.

    PubMed

    Flynn, Francis J; Schaumberg, Rebecca L

    2012-01-01

    The authors posit that higher levels of guilt-proneness are associated with higher levels of affective organizational commitment. To explain this counterintuitive link, the authors suggest that a dispositional tendency to feel guilt motivates individuals to exert greater effort on their work-related tasks that, in turn, strengthens their affinity for the organization. The authors tested this idea using a laboratory study and field data from 2 samples of working adults. Individuals who are more guilt-prone reported higher levels of organizational attachment compared with less guilt-prone individuals. Furthermore, mediation analyses indicate that the link between guilt-proneness and affective commitment is driven by greater task effort. The authors discuss the implications of these findings for understanding the affective drivers of commitment in organizations.

  17. ECG Segmentation and P-Wave Feature Extraction: Application to Patients Prone to Atrial Fibrillation

    DTIC Science & Technology

    2007-11-02

    detection of patients prone to atrial fibrillation (AF), one of the most frequent arrhythmias. It focuses first on the segmentation of the...Keywords : atrial fibrillation , ECG segmentation, P-wave, hidden Markov model, wavelets, ECG database I. INTRODUCTION Atrial fibrillation (AF) is a very... atrial thrombosis, with the subsequent risk of a stroke. The aim of this study is to try to automatically detect patients prone to atrial fibrillation (AF

  18. Prone position in acute respiratory distress syndrome. Rationale, indications, and limits.

    PubMed

    Gattinoni, Luciano; Taccone, Paolo; Carlesso, Eleonora; Marini, John J

    2013-12-01

    In the prone position, computed tomography scan densities redistribute from dorsal to ventral as the dorsal region tends to reexpand while the ventral zone tends to collapse. Although gravitational influence is similar in both positions, dorsal recruitment usually prevails over ventral derecruitment, because of the need for the lung and its confining chest wall to conform to the same volume. The final result of proning is that the overall lung inflation is more homogeneous from dorsal to ventral than in the supine position, with more homogeneously distributed stress and strain. As the distribution of perfusion remains nearly constant in both postures, proning usually improves oxygenation. Animal experiments clearly show that prone positioning delays or prevents ventilation-induced lung injury, likely due in large part to more homogeneously distributed stress and strain. Over the last 15 years, five major trials have been conducted to compare the prone and supine positions in acute respiratory distress syndrome, regarding survival advantage. The sequence of trials enrolled patients who were progressively more hypoxemic; exposure to the prone position was extended from 8 to 17 hours/day, and lung-protective ventilation was more rigorously applied. Single-patient and meta-analyses drawing from the four major trials showed significant survival benefit in patients with PaO2/FiO2 lower than 100. The latest PROSEVA (Proning Severe ARDS Patients) trial confirmed these benefits in a formal randomized study. The bulk of data indicates that in severe acute respiratory distress syndrome, carefully performed prone positioning offers an absolute survival advantage of 10-17%, making this intervention highly recommended in this specific population subset.

  19. Exploring the relationship between boredom proneness and self-control in traumatic brain injury (TBI).

    PubMed

    Isacescu, Julia; Danckert, James

    2016-05-23

    Characterized as an agitated state in which the individual is motivated to engage in their environment but all attempts to do so fail to satisfy, boredom represents a disengaged attentional state that is associated with negative affect and poor self-control. There have been anecdotal reports of increased levels of boredom post-traumatic brain injury (TBI). For the first time, we provide objective evidence that TBI patients do indeed experience higher levels of boredom proneness. Hierarchical regression analyses showed that the presence and severity of head injury were a significant positive predictor of levels of boredom proneness and a negative predictor of self-control. As with healthy controls, TBI patients showed a strong negative correlation between boredom proneness and self-control-those with lower levels of self-control exhibited higher levels of boredom proneness. This was despite the fact that our TBI patients reported higher overall levels of self-control (probably concomitant with their older mean age). The TBI patients also showed strong positive correlations between boredom proneness and measures of physical aggression and anger. Together, this suggests that patients with TBI may be more susceptible to increased levels of boredom proneness and other negative affective states that arise as a consequence of failures of self-control.

  20. An analysis on muscle tone and stiffness during sling exercise on static prone position

    PubMed Central

    Kim, Jeong-Ja

    2016-01-01

    [Purpose] The purpose of this study was to examine changes in the muscle tone and stiffness of the lumbar region while individuals adopted the static prone position using sling suspension. [Subjects and Methods] The subjects were 30 healthy women in their 20s. The muscle tone and stiffness of the upper and lower lumbar regions of the sling suspension group and a control group were measured using myotonmetory as they maintained the static prone positon. [Results] The sling suspension group showed statistically significant declines in the muscle tone and stiffness of the upper lumbar region 5–10 min after adopting the initial prone position. They also showed statistically significant declines in the muscle tone and stiffness of the lower lumbar region immediately after being suspended in the slings and a statistically significant decline in the muscle tone of the lower lumbar region 5–10 min after adopting the initial prone position during which the sling suspension was applied. In contrast, the muscle tone and stiffness of the lumbar region of the control group increased while maintaining the static prone position. [Conclusion] The static prone position performed on a treatment table using sling suspension can be an effective intervention for reducing the muscle tone and stiffness of the lumbar region. PMID:28174469

  1. Vocational interests and career indecision among psychosis-prone college students.

    PubMed

    Poreh, A M; Schullen, C

    1998-10-01

    This study investigated the relationship between scores on scales that purport to measure psychosis-proneness and scores on vocational interests, identity, and differentiation scales in a sample of 233 college students who completed the Perceptual Aberration and Magical Ideation scales, the Strong Campbell Interest Inventory, and the Career Decision Scale. The present findings are consistent with prior work indicating a sex-related association of scores on measures of psychosis-proneness and vocational interests. A positive correlation between scores on vocational indecision and measures of psychosis-proneness was also found, suggesting that both men and women who score high on psychosis-proneness find it difficult to formulate long-term career goals. Finally, there was no significant correlation between scores on measures of psychosis-proneness and Holland's Vocational Differentiation Index. Present results are discussed in light of previously reported sex differences among psychosis-prone adults and diagnosed schizophrenics. The implications of the findings for vocational counselors are also addressed.

  2. Delusion proneness in nonclinical individuals and cognitive insight: the contributions of rumination and reflection.

    PubMed

    Carse, Traci; Langdon, Robyn

    2013-08-01

    Although previous research demonstrates that clinical individuals with delusions score low on one of the facets of cognitive insight, self-reflection, and high on the other facet, self-certainty, analogous studies of delusion proneness in nonclinical individuals have found that delusion proneness in nonclinical individuals associates with higher levels of both self-certainty and self-reflection. The present study sought to reconcile these inconsistent results by examining the contributions of different facets of self-reflection, rumination and reflection, to delusion proneness. One hundred fifty-two individuals completed three questionnaires: the Beck Cognitive Insight Scale (BCIS), the Peters et al. Delusions Inventory (PDI), and the Rumination-Reflection Questionnaire (RRQ). The results showed that the individuals scoring higher on delusion proneness demonstrated higher levels of both self-certainty and self-reflection on the BCIS as well as higher levels of rumination and reflection on the RRQ. As predicted, the strength of the relationship between BCIS self-reflection and delusion proneness was diminished when rumination was controlled for. These findings suggest that the previously observed positive relation between BCIS self-reflection and nonclinical delusion proneness might be driven, in part, by the ruminative aspect of self-reflection.

  3. Design and Evaluation of a Stand-Up Motorized Prone Cart

    PubMed Central

    Harrow, Jeffrey J; Malassigné, Pascal; Nelson, Audrey L; Jensen, Robert P; Amato, Margaret; Palacios, Polly L

    2007-01-01

    Background/Objective: Prone carts are used for mobility by individuals with spinal cord injury in whom seated mobility (wheelchair) is contraindicated due to ischial or sacral pressure ulcers. Currently available prone carts are uncomfortable, subjecting the user to neck and shoulder strain, and make social interaction and performing activities of daily living difficult. A better design of prone carts is needed. In addition, standing devices have shown some medical benefits. The objective was to design and evaluate an improved prone cart that facilitates standing. Design: Engineering development project with user feedback through questionnaire. Users selected by convenience sampling. Methods: A marketing survey was performed of nurse managers of spinal cord injury units. Then 2 prototype carts were designed and built. These carts are able to tilt up to 45° and have a joystick-controlled motor for propulsion and other design features, including a workspace storage shelf and rearview mirrors. The carts were evaluated by both patients and caregivers at 2 Veteran's Administration hospitals. Outcome Measures: Questionnaire of subjects, both patients and caregivers, who used the cart. Findings: Both patients and caregivers liked the carts and the ability to assume a nonhorizontal body angle. The major complaint about the cart was that it seemed too long when it came to making turns. Conclusion: This prone cart design is an improvement over the standard, flat variety. However, further design changes will be necessary. This study provided valuable information that will be useful in the next-generation prone cart design project. PMID:17385270

  4. Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review

    PubMed Central

    Koulouras, Vasilios; Papathanakos, Georgios; Papathanasiou, Athanasios; Nakos, Georgios

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the “sponge lung” - and the “shape matching” -model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients’ response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort. PMID:27152255

  5. Children’s Proneness to Shame and Guilt Predict Risky and Illegal Behaviors in Young Adulthood

    PubMed Central

    Stuewig, Jeffrey; Tangney, June P.; Kendall, Stephanie; Folk, Johanna B.; Meyer, Candace Reinsmith; Dearing, Ronda L.

    2014-01-01

    Do shame and guilt help people avoid doing wrong? Although some research suggests that guilt-proneness is a protective factor while shame-proneness puts individuals at risk, most research is either cross-sectional or short-term. In this longitudinal study, 380 5th graders (ages 10–12) completed measures of proneness to shame and guilt. We re-interviewed 68% of participants after they turned 18 years old (range 18–21). Guilt-proneness assessed in childhood predicted fewer sexual partners, less use of illegal drugs and alcohol, and less involvement with the criminal justice system. Shame-proneness, in contrast, was a risk factor for later deviant behavior. Shame-prone children were more likely to have unprotected sex and use illegal drugs in young adulthood. These results held when controlling for childhood SES and teachers’ ratings of aggression. Children’s moral emotional styles appear to be well established by at least middle childhood, with distinct downstream implications for risky behavior in early adulthood. PMID:24842762

  6. High fat diet increases and the polyphenol, S17834, decreases acetylation of the SirT1-dependent lysine-382 on p53 and apoptotic signaling in atherosclerotic lesion-prone aortic endothelium of normal mice

    PubMed Central

    Xu, Shanqin; Jiang, Bingbing; Hou, Xiuyun; Shi, Chaomei; Bachschmid, Markus; Zang, Mengwei; Verbeuren, Tony J.; Cohen, Richard A.

    2011-01-01

    Our purpose was to determine if high fat diet and treatment with a polyphenol regulates acetylation of lysine-382 of p53, the site regulated by sirtuin-1, and apoptosis in the endothelium of the atherosclerotic lesion-prone mouse aortic arch. In cultured endothelial cells two atherogenic stimuli, hydrogen peroxide and tumor necrosis factor-α, increased acetylation of p53 lysine-382, as well as caspase-3 cleavage, an indicator of apoptotic signaling. The polyphenol, S17834, significantly prevented these changes. In LDL receptor-deficient mice, a high fat diet increased, and treatment with S17834 attenuated early atherosclerotic lesions on the lesser curvature of the aortic arch. In wild type C57BL6 mice fed the same diet, no atherosclerotic lesions were observed in this lesion-prone area, but p53 acetylation and caspase-3 cleavage increased in the endothelium. In high fat fed mice, S17834 increased sirtuin-1 protein in the lesion-prone endothelium and prevented both the increase in p53 acetylation and caspase-3 cleavage without affecting blood lipids. These results indicate that high fat diet increases and S17834 decreases acetylation of p53 in lesion-prone aortic endothelial cells of normal mice independently of blood lipids, suggesting that the polyphenol may regulate endothelial cell p53 acetylation and apoptosis via local actions. PMID:21654327

  7. Back analysis of fault-slip in burst prone environment

    NASA Astrophysics Data System (ADS)

    Sainoki, Atsushi; Mitri, Hani S.

    2016-11-01

    In deep underground mines, stress re-distribution induced by mining activities could cause fault-slip. Seismic waves arising from fault-slip occasionally induce rock ejection when hitting the boundary of mine openings, and as a result, severe damage could be inflicted. In general, it is difficult to estimate fault-slip-induced ground motion in the vicinity of mine openings because of the complexity of the dynamic response of faults and the presence of geological structures. In this paper, a case study is conducted for a Canadian underground mine, herein called "Mine-A", which is known for its seismic activities. Using a microseismic database collected from the mine, a back analysis of fault-slip is carried out with mine-wide 3-dimensional numerical modeling. A back analysis is conducted to estimate the physical and mechanical properties of the causative fracture or shear zones. One large seismic event has been selected for the back analysis to detect a fault-slip related seismic event. In the back analysis, the shear zone properties are estimated with respect to moment magnitude of the seismic event and peak particle velocity (PPV) recorded by a strong ground motion sensor. The estimated properties are then validated through comparison with peak ground acceleration recorded by accelerometers. Lastly, ground motion in active mining areas is estimated by conducting dynamic analysis with the estimated values. The present study implies that it would be possible to estimate the magnitude of seismic events that might occur in the near future by applying the estimated properties to the numerical model. Although the case study is conducted for a specific mine, the developed methodology can be equally applied to other mines suffering from fault-slip related seismic events.

  8. Accelerating Particles with Plasma

    ScienceCinema

    Litos, Michael; Hogan, Mark

    2016-07-12

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  9. Peak acceleration limiter

    NASA Technical Reports Server (NTRS)

    Chapman, C. P.

    1972-01-01

    Device is described that limits accelerations by shutting off shaker table power very rapidly in acceleration tests. Absolute value of accelerometer signal is used to trigger electronic switch which terminates test and sounds alarm.

  10. Linear Accelerator (LINAC)

    MedlinePlus

    ... equipment? How is safety ensured? What is this equipment used for? A linear accelerator (LINAC) is the ... Therapy (SBRT) . top of page How does the equipment work? The linear accelerator uses microwave technology (similar ...

  11. Accelerating Particles with Plasma

    SciTech Connect

    Litos, Michael; Hogan, Mark

    2014-11-05

    Researchers at SLAC explain how they use plasma wakefields to accelerate bunches of electrons to very high energies over only a short distance. Their experiments offer a possible path for the future of particle accelerators.

  12. Improved plasma accelerator

    NASA Technical Reports Server (NTRS)

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  13. Accelerator Technology Division

    NASA Astrophysics Data System (ADS)

    1992-04-01

    In fiscal year (FY) 1991, the Accelerator Technology (AT) division continued fulfilling its mission to pursue accelerator science and technology and to develop new accelerator concepts for application to research, defense, energy, industry, and other areas of national interest. This report discusses the following programs: The Ground Test Accelerator Program; APLE Free-Electron Laser Program; Accelerator Transmutation of Waste; JAERI, OMEGA Project, and Intense Neutron Source for Materials Testing; Advanced Free-Electron Laser Initiative; Superconducting Super Collider; The High-Power Microwave Program; (Phi) Factory Collaboration; Neutral Particle Beam Power System Highlights; Accelerator Physics and Special Projects; Magnetic Optics and Beam Diagnostics; Accelerator Design and Engineering; Radio-Frequency Technology; Free-Electron Laser Technology; Accelerator Controls and Automation; Very High-Power Microwave Sources and Effects; and GTA Installation, Commissioning, and Operations.

  14. Severe Tissue Trauma Triggers the Autoimmune State Systemic Lupus Erythematosus in the MRL/++ Lupus-Prone Mouse

    DTIC Science & Technology

    2009-01-01

    extending from the epidermis to the subcutis with abnor- mal hair follicle proliferation (data not shown). On the contrary, no such lesions were...New Jersey, USA) to remove remaining hair stubble. Using a surgical skin marker, a l5-mm diameter circular area along the dor- sal rrUdline region was...than one site and 3 = large, more than two sites). Proteinuria Urine was tested for proteinuria using commercially available kits (Multistix, Bayer

  15. Accelerators, Colliders, and Snakes

    NASA Astrophysics Data System (ADS)

    Courant, Ernest D.

    2003-12-01

    The author traces his involvement in the evolution of particle accelerators over the past 50 years. He participated in building the first billion-volt accelerator, the Brookhaven Cosmotron, which led to the introduction of the "strong-focusing" method that has in turn led to the very large accelerators and colliders of the present day. The problems of acceleration of spin-polarized protons are also addressed, with discussions of depolarizing resonances and "Siberian snakes" as a technique for mitigating these resonances.

  16. Effects of salvianolate on bone metabolism in glucocorticoid-treated lupus-prone B6.MRL-Faslpr/J mice

    PubMed Central

    Liu, Yanzhi; Cui, Yang; Zhang, Xiao; Gao, Xiang; Su, Yanjie; Xu, Bilian; Wu, Tie; Chen, Wenshuang; Cui, Liao

    2016-01-01

    Aim To investigate the bone-protective effects of salvianolate (Sal), a total polyphenol from Radix Salviae miltiorrhizae, on bone tissue in the spontaneous lupus-prone mouse model, B6.MRL-Faslpr/J, undergoing glucocorticoid (GC) treatment. Methods Fifteen-week-old female B6.MRL-Faslpr/J mice were administered either a daily dose of saline (lupus group), prednisone 6 mg/kg (GC group), Sal 60 mg/kg (Sal group); or GC plus Sal (GC + Sal group) for a duration of 12 weeks. Age-matched female C57BL/6J wild-type (WT) mice were used for control. Micro-computed tomography assessments, bone histomorphometry analysis, bone biomechanical test, immunohistochemistry and immunoblotting analysis for bone markers, and renal histology analysis were performed to support our research endeavor. Results Lupus mice developed a marked bone loss and deterioration of mechanical properties of bone due to an increase in bone resorption rather than suppression of bone formation. GC treatment strongly inhibited bone formation in lupus mice. Sal treatment significantly attenuated osteogenic inhibition, and also suppressed hyperactive bone resorption, which recovered the bone mass and mechanical properties of bone in both the untreated and GC-treated lupus mice. Conclusion The data support further preclinical investigation of Sal as a potential therapeutic strategy for the treatment of systemic lupus erythematosus-related bone loss. PMID:27563234

  17. Acceleration: It's Elementary

    ERIC Educational Resources Information Center

    Willis, Mariam

    2012-01-01

    Acceleration is one tool for providing high-ability students the opportunity to learn something new every day. Some people talk about acceleration as taking a student out of step. In actuality, what one is doing is putting a student in step with the right curriculum. Whole-grade acceleration, also called grade-skipping, usually happens between…

  18. Angular Acceleration without Torque?

    ERIC Educational Resources Information Center

    Kaufman, Richard D.

    2012-01-01

    Hardly. Just as Robert Johns qualitatively describes angular acceleration by an internal force in his article "Acceleration Without Force?" here we will extend the discussion to consider angular acceleration by an internal torque. As we will see, this internal torque is due to an internal force acting at a distance from an instantaneous center.

  19. Accelerated test design

    NASA Technical Reports Server (NTRS)

    Mcdermott, P. P.

    1980-01-01

    The design of an accelerated life test program for electric batteries is discussed. A number of observations and suggestions on the procedures and objectives for conducting an accelerated life test program are presented. Equations based on nonlinear regression analysis for predicting the accelerated life test parameters are discussed.

  20. Having fun with a cordless mouse

    NASA Astrophysics Data System (ADS)

    Nunn, John

    2016-07-01

    A cordless mouse with an added reed switch is used as a wireless data logger to record every time the wheel of a trolley completes a revolution. The limitations of the system in terms of maximum clicking rate and spatial resolution are considered and data obtained from the descent of a trolley down a ramp at various different angles is analysed in different ways. The data is analysed to obtain initial accelerations (down the ramp) and subsequent decelerations (on the flat), as well as maximum velocities, and these results are used to compare the actual performance of the trolley (with friction) with the theoretical expectation. An agreement of better than 2% on the value of gravity is obtained. Encouraging agreement on frictional forces (and accelerations) is also obtained by considering the maximum kinetic energies reached at the bottom of the ramp. This paper includes the free provision of custom software to record the time history of the clicking of a mouse.

  1. Whole-breast irradiation: a subgroup analysis of criteria to stratify for prone position treatment

    SciTech Connect

    Ramella, Sara; Trodella, Lucio; Ippolito, Edy; Fiore, Michele; Cellini, Francesco; Stimato, Gerardina; Gaudino, Diego; Greco, Carlo; Ramponi, Sara; Cammilluzzi, Eugenio; Cesarini, Claudio; Piermattei, Angelo; Cesario, Alfredo; D'Angelillo, Rolando Maria

    2012-07-01

    To select among breast cancer patients and according to breast volume size those who may benefit from 3D conformal radiotherapy after conservative surgery applied with prone-position technique. Thirty-eight patients with early-stage breast cancer were grouped according to the target volume (TV) measured in the supine position: small ({<=}400 mL), medium (400-700 mL), and large ({>=}700 ml). An ad-hoc designed and built device was used for prone set-up to displace the contralateral breast away from the tangential field borders. All patients underwent treatment planning computed tomography in both the supine and prone positions. Dosimetric data to explore dose distribution and volume of normal tissue irradiated were calculated for each patient in both positions. Homogeneity index, hot spot areas, the maximum dose, and the lung constraints were significantly reduced in the prone position (p < 0.05). The maximum heart distance and the V{sub 5Gy} did not vary consistently in the 2 positions (p = 0.06 and p = 0.7, respectively). The number of necessary monitor units was significantly higher in the supine position (312 vs. 232, p < 0.0001). The subgroups analysis pointed out the advantage in lung sparing in all TV groups (small, medium and large) for all the evaluated dosimetric constraints (central lung distance, maximum lung distance, and V{sub 5Gy}, p < 0.0001). In the small TV group, a dose reduction in nontarget areas of 22% in the prone position was detected (p = 0.056); in the medium and high TV groups, the difference was of about -10% (p = NS). The decrease in hot spot areas in nontarget tissues was 73%, 47%, and 80% for small, medium, and large TVs in the prone position, respectively. Although prone breast radiotherapy is normally proposed in patients with breasts of large dimensions, this study gives evidence of dosimetric benefit in all patient subgroups irrespective of breast volume size.

  2. Analyses of mRNA Profiling through RNA Sequencing on a SAMP8 Mouse Model in Response to Ginsenoside Rg1 and Rb1 Treatment

    PubMed Central

    Zhang, Shuai; Zhu, Dina; Li, Hong; Zhang, Haijing; Feng, Chengqiang; Zhang, Wensheng

    2017-01-01

    Ginsenoside Rg1 and Rb1 are the major ingredients in two medicines called QiShengLi (Z20027165) and QiShengJing (Z20027164) approved by China. These ingredients are believed to mitigate forgetfulness. Numerous studies have confirmed that GRg1 and GRb1 offer protection against Alzheimer's disease (AD), and our morris water maze (MWM) experiment also indicated that GRg1 and GRb1 may attenuate memory deficits in the 7-month-old SAMP8 mice; however, comprehensive understanding of their roles in AD remains limited. This study systematically explored the mechanism at the genome level of the anti-AD effects of GRg1 and GRb1 in a senescence-accelerated mouse prone 8 (SAMP8) model through deep RNA sequencing. A total of 74,885 mRNA transcripts were obtained. Expression analysis showed that 1,780 mRNA transcripts were differentially expressed in SAMP8 mice compared with the SAMP8+GRg1 mice. Moreover, 1,066 significantly dysregulated mRNA transcripts were identified between SAMP8 and SAMP8+GRb1 mice. Analyses according to gene ontology and the Kyoto Encyclopedia of Genes and Genomes revealed that oral administration of GRg1 and GRb1 improved the learning performance of the SAMP8 mouse model from various aspects, such as nervous system development and mitogen-activated protein kinase signaling pathway. The most probable AD-related transcriptional responses after medication were predicted and discussed in detail. This study is the first to provide a systematic dissection of mRNA profiling in SAMP8 mouse brain in response to GRg1 and GRb1 treatment. We explained their efficacy thoroughly from the source (gene-level explanation). The findings serve as a theoretical basis for the exploration of GRg1 and GRb1 as functional drugs with anti-AD activity. PMID:28289387

  3. Mouse homologues of human hereditary disease.

    PubMed Central

    Searle, A G; Edwards, J H; Hall, J G

    1994-01-01

    Details are given of 214 loci known to be associated with human hereditary disease, which have been mapped on both human and mouse chromosomes. Forty two of these have pathological variants in both species; in general the mouse variants are similar in their effects to the corresponding human ones, but exceptions include the Dmd/DMD and Hprt/HPRT mutations which cause little, if any, harm in mice. Possible reasons for phenotypic differences are discussed. In most pathological variants the gene product seems to be absent or greatly reduced in both species. The extensive data on conserved segments between human and mouse chromosomes are used to predict locations in the mouse of over 50 loci of medical interest which are mapped so far only on human chromosomes. In about 80% of these a fairly confident prediction can be made. Some likely homologies between mapped mouse loci and unmapped human ones are also given. Sixty six human and mouse proto-oncogene and growth factor gene homologies are also listed; those of confirmed location are all in known conserved segments. A survey of 18 mapped human disease loci and chromosome regions in which the manifestation or severity of pathological effects is thought to be the result of genomic imprinting shows that most of the homologous regions in the mouse are also associated with imprinting, especially those with homologues on human chromosomes 11p and 15q. Useful methods of accelerating the production of mouse models of human hereditary disease include (1) use of a supermutagen, such as ethylnitrosourea (ENU), (2) targeted mutagenesis involving ES cells, and (3) use of gene transfer techniques, with production of 'knockout mutations'. PMID:8151633

  4. Fiber Accelerating Structures

    SciTech Connect

    Hammond, Andrew P.; /Reed Coll. /SLAC

    2010-08-25

    One of the options for future particle accelerators are photonic band gap (PBG) fiber accelerators. PBG fibers are specially designed optical fibers that use lasers to excite an electric field that is used to accelerate electrons. To improve PBG accelerators, the basic parameters of the fiber were tested to maximize defect size and acceleration. Using the program CUDOS, several accelerating modes were found that maximized these parameters for several wavelengths. The design of multiple defects, similar to having closely bound fibers, was studied to find possible coupling or the change of modes. The amount of coupling was found to be dependent on distance separated. For certain distances accelerating coupled modes were found and examined. In addition, several non-periodic fiber structures were examined using CUDOS. The non-periodic fibers produced several interesting results and promised more modes given time to study them in more detail.

  5. High brightness electron accelerator

    DOEpatents

    Sheffield, Richard L.; Carlsten, Bruce E.; Young, Lloyd M.

    1994-01-01

    A compact high brightness linear accelerator is provided for use, e.g., in a free electron laser. The accelerator has a first plurality of acclerating cavities having end walls with four coupling slots for accelerating electrons to high velocities in the absence of quadrupole fields. A second plurality of cavities receives the high velocity electrons for further acceleration, where each of the second cavities has end walls with two coupling slots for acceleration in the absence of dipole fields. The accelerator also includes a first cavity with an extended length to provide for phase matching the electron beam along the accelerating cavities. A solenoid is provided about the photocathode that emits the electons, where the solenoid is configured to provide a substantially uniform magnetic field over the photocathode surface to minimize emittance of the electons as the electrons enter the first cavity.

  6. Hip rotation range of motion in sitting and prone positions in healthy Japanese adults

    PubMed Central

    Han, Heonsoo; Kubo, Akira; Kurosawa, Kazuo; Maruichi, Shizuka; Maruyama, Hitoshi

    2015-01-01

    [Purpose] The aim of this study was to elucidate the difference in hip external and internal rotation ranges of motion (ROM) between the prone and sitting positions. [Subjects] The subjects included 151 students. [Methods] Hip rotational ROM was measured with the subjects in the prone and sitting positions. Two-way repeated measures analysis of variance (ANOVA) was used to analyze ipsilateral hip rotation ROM in the prone and sitting positions in males and females. The total ipsilateral hip rotation ROM was calculated by adding the measured values for external and internal rotations. [Results] Ipsilateral hip rotation ROM revealed significant differences between two positions for both left and right internal and external rotations. Hip rotation ROM was significantly higher in the prone position than in the sitting position. Hip rotation ROM significantly differed between the men and women. Hip external rotation ROM was significantly higher in both positions in men; conversely, hip internal rotation ROM was significantly higher in both positions in women. [Conclusion] Hip rotation ROM significantly differed between the sexes and between the sitting and prone positions. Total ipsilateral hip rotation ROM, total angle of external rotation, and total angle of internal rotation of the left and right hips greatly varied, suggesting that hip joint rotational ROM is widely distributed. PMID:25729186

  7. Relationship between childhood trauma, mindfulness, and dissociation in subjects with and without hallucination proneness.

    PubMed

    Perona-Garcelán, Salvador; García-Montes, José M; Rodríguez-Testal, Juan Francisco; López-Jiménez, Ana Ma; Ruiz-Veguilla, Miguel; Ductor-Recuerda, María Jesús; Benítez-Hernández, María del Mar; Arias-Velarde, Ma Ángeles; Gómez-Gómez, María Teresa; Pérez-Álvarez, Marino

    2014-01-01

    The purpose of this study was to examine the relationship between childhood traumas, mindfulness, and dissociation (more specifically, absorption and depersonalization) in healthy subjects with and without hallucination proneness. A sample of 318 subjects was given the Launay-Slade Hallucination Scale-Revised (R. P. Bentall & P. Slade, 1985). From this sample, 2 groups were formed: one with high and the other with low hallucination proneness. Furthermore, all participants were given the Tellegen Absorption Scale (A. Tellegen & G. Atkinson, 1974), the Cambridge Depersonalization Scale (M. Sierra & G. E. Berrios, 2000), the Southampton Mindfulness Questionnaire (P. D. J. Chadwick et al., 2008), and the Trauma Questionnaire (J. R. E. Davidson, D. Hughes, & D. G. Blazer, 1990). The results showed that in the group with high hallucination proneness, there were significantly more subjects with traumatic experiences than in the group with low predisposition, although no significant difference in the mean number of traumatic experiences undergone in childhood was found between the 2 groups, although there was a trend toward significance. A correlation analysis showed a significant negative association between mindfulness on the one hand and absorption and depersonalization on the other. A positive relationship was also found between childhood traumas and absorption and depersonalization. Finally, multiple mediation analysis showed that the absorption and depersonalization variables acted as mediators between childhood traumas and hallucination proneness. We discuss the importance of the relationship between the variables studied and hallucination proneness and suggest some approaches for their treatment.

  8. Aggregate-prone desmin mutations impair mitochondrial calcium uptake in primary myotubes.

    PubMed

    Smolina, Natalia; Bruton, Joseph; Sjoberg, Gunnar; Kostareva, Anna; Sejersen, Thomas

    2014-10-01

    Desmin, being a major intermediate filament of mature muscle cell, interacts with mitochondria within the cell and participates in mitochondria proper localization. The goal of the present study was to assess the effect of aggregate-prone and non-aggregate-prone desmin mutations on mitochondrial calcium uptake. Primary murine satellite cells were transduced with lentiviruses carrying desmin in wild type or mutant form, and were induced to differentiate into myotubes. Four mutations resulting in different degree of desmin aggregates formation were analyzed. Tail domain mutation Asp399Tyr has the mildest impact on desmin filament polymerization, rod domain mutation Ala357Pro causes formation of large aggregates composed of filamentous material, and Leu345Pro and Leu370Pro are considered to be the most severest in their impact on desmin polymerization and structure. For mitochondrial calcium measurement cells were loaded with rhod 2-AM. We found that aggregate-prone mutations significantly decreased [Ca(2+)]mit, whereas non-aggregate-prone mutations did not decrease [Ca(2+)]mit. Moreover aggregate-prone desmin mutations resulted in increased resting cytosolic [Ca(2+)]. However this increase was not accompanied by any alterations in sarcoplasmic reticulum calcium release. We suggest that the observed decline in [Ca(2+)]mit was due to desmin aggregate accumulation resulting in the loss of desmin mitochondria interactions.

  9. Perceived threat mediates the relationship between psychosis proneness and aggressive behavior.

    PubMed

    Fanning, Jennifer Renee; Berman, Mitchell Eric; Mohn, Richard Samuel; McCloskey, Michael Sean

    2011-04-30

    Psychotic symptoms are associated with aggressive tendencies, but this relationship is both complex and imperfect. In contrast to psychotic disorders, little is known about aggressive behavior and sub-clinical psychotic symptoms (e.g., "psychosis proneness"), which are relatively common in the general population. Threat/control-override (TCO), which is the propensity to overestimate the likelihood that an outside agent will (1) inflict harm (threat) or (2) control one's behaviors (control-override), has been associated with aggression in both psychiatric and community samples. The purpose of this study was to determine if psychosis proneness is related to aggression, and if one or both aspects of TCO mediate this relationship. We hypothesized that the propensity to overestimate threat would mediate this relationship, but control-override would not. Sixty men and sixty women (mean age=20.00 years, sd=3.00) with no history of psychotic disorder completed measures assessing psychosis proneness, threat control/override, aggressive history, aggressive ideation, and aggressive behavior. Three structural equation models were tested: (1) Threat and control-override modeled as separate mediating variables, (2) TCO as a unitary mediating latent construct, and (3) TCO considered as part of a psychosis proneness latent variable. Results indicated that psychosis proneness is positively related to aggression and that the best model fit was obtained when threat and control-override were modeled as separate variables, with mediation through threat alone. The utility of TCO for explaining the relation between psychosis spectrum symptoms and aggression is discussed.

  10. Clarifying the Link Between Job Satisfaction and Absenteeism: The Role of Guilt Proneness.

    PubMed

    Schaumberg, Rebecca L; Flynn, Francis J

    2017-03-09

    We propose that the relationship between job satisfaction and absenteeism depends partly on guilt proneness. Drawing on withdrawal and process models of absenteeism, we argue that job satisfaction predicts absences for employees who are low (but not high) in guilt proneness because low guilt-prone people's behaviors are governed more by fulfilling their own egoistic desires than by fulfilling others' normative expectations. We find support for this prediction in a sample of customer service agents working for a major telecommunications company and a sample of working adults employed in a range of industries. In each study, we use measures of employees' guilt proneness and job satisfaction to predict their subsequent workplace absences. In Study 2, we extend our hypothesis tests to 2 traits that are conceptually comparable to guilt proneness (i.e., moral identity and agreeableness), showing that these traits similarly moderate the relationship between job satisfaction and absenteeism. We discuss the implications of these findings for extant models of absenteeism and research on moral affectivity in the workplace. (PsycINFO Database Record

  11. Acceleration in astrophysics

    SciTech Connect

    Colgate, S.A.

    1993-12-31

    The origin of cosmic rays and applicable laboratory experiments are discussed. Some of the problems of shock acceleration for the production of cosmic rays are discussed in the context of astrophysical conditions. These are: The presumed unique explanation of the power law spectrum is shown instead to be a universal property of all lossy accelerators; the extraordinary isotropy of cosmic rays and the limited diffusion distances implied by supernova induced shock acceleration requires a more frequent and space-filling source than supernovae; the near perfect adiabaticity of strong hydromagnetic turbulence necessary for reflecting the accelerated particles each doubling in energy roughly 10{sup 5} to {sup 6} scatterings with negligible energy loss seems most unlikely; the evidence for acceleration due to quasi-parallel heliosphere shocks is weak. There is small evidence for the expected strong hydromagnetic turbulence, and instead, only a small number of particles accelerate after only a few shock traversals; the acceleration of electrons in the same collisionless shock that accelerates ions is difficult to reconcile with the theoretical picture of strong hydromagnetic turbulence that reflects the ions. The hydromagnetic turbulence will appear adiabatic to the electrons at their much higher Larmor frequency and so the electrons should not be scattered incoherently as they must be for acceleration. Therefore the electrons must be accelerated by a different mechanism. This is unsatisfactory, because wherever electrons are accelerated these sites, observed in radio emission, may accelerate ions more favorably. The acceleration is coherent provided the reconnection is coherent, in which case the total flux, as for example of collimated radio sources, predicts single charge accelerated energies much greater than observed.

  12. Mouse Curve Biometrics

    SciTech Connect

    Schulz, Douglas A.

    2007-10-08

    A biometric system suitable for validating user identity using only mouse movements and no specialized equipment is presented. Mouse curves (mouse movements with little or no pause between them) are individually classied and used to develop classication histograms, which are representative of an individual's typical mouse use. These classication histograms can then be compared to validate identity. This classication approach is suitable for providing continuous identity validation during an entire user session.

  13. IL-10 Production Is Critical for Sustaining the Expansion of CD5+ B and NKT Cells and Restraining Autoantibody Production in Congenic Lupus-Prone Mice

    PubMed Central

    Baglaenko, Yuriy; Manion, Kieran P.; Chang, Nan-Hua; Gracey, Eric; Loh, Christina; Wither, Joan E.

    2016-01-01

    The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB) strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT) cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B cells but not NKT cells derived from these mice could suppress the development of pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics that leads to expansion of these two innate-like populations through the creation of additional sub-congenic mice and to characterize the role of IL-10 in the suppression of autoimmunity through the generation of IL-10 knockout mice. We show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4 interval spanning 91 to 123 Mb, which is distinct from the region that mediates the majority of the suppressive phenotype. We also demonstrate that IL-10 is critical to restraining autoantibody production and surprisingly plays a vital role in supporting the expansion of innate-like populations. PMID:26964093

  14. Beneficial effect of the inosine monophosphate dehydrogenase inhibitor mycophenolate mofetil on survival and severity of glomerulonephritis in systemic lupus erythematosus (SLE)-prone MRLlpr/lpr mice

    PubMed Central

    Jonsson, C A; Svensson, L; Carlsten, H

    1999-01-01

    The aim of the present study was to evaluate the therapeutic effect of mycophenolate mofetil (MMF) on the course of disease in SLE-prone MRLlpr/lpr mice. Three-months-old mice displaying clinical symptoms of glomerulonephritis were given MMF (100 mg/kg per day) orally via the drinking water. Control mice received i.p. injections of cyclophosphamide (CYC) (1.8 mg/mouse per week) or saline. Survival, albuminuria and haematuria, immunoglobulin levels and anti-dsDNA antibodies in serum, frequencies of immunoglobulin-producing B lymphocytes and glomerular deposits of immunoglobulin and C3 were analysed. The results showed that MMF treatment significantly prolonged survival and reduced the occurrence of albuminuria and haematuria in MRLlpr/lpr mice. In addition, the number of immunoglobulin-producing B cells and serum levels of IgG and IgG anti-dsDNA antibodies were reduced after MMF and CYC treatment. MMF treatment significantly reduced the extent of deposition of C3 in glomeruli. We conclude that the reduced severity of glomerulonephritis following treatment of lupus-prone mice with MMF was as efficacious as that of CYC. These results warrant clinical trials of MMF in SLE patients with glomerulonephritis. PMID:10361247

  15. Building a Brainier Mouse.

    ERIC Educational Resources Information Center

    Tsien, Joe Z.

    2000-01-01

    Describes a genetic engineering project to build an intelligent mouse. Cites understanding the molecular basis of learning and memory as a very important step. Concludes that while science will never create a genius mouse that plays the stock market, it can turn a mouse into a quick learner with a better memory. (YDS)

  16. Evidence for accelerated tauopathy in the retina of transgenic P301S tau mice exposed to repetitive mild traumatic brain injury.

    PubMed

    Xu, Leyan; Ryu, Jiwon; Nguyen, Judy V; Arena, John; Rha, Elizabeth; Vranis, Pamela; Hitt, Devon; Marsh-Armstrong, Nicholas; Koliatsos, Vassilis E

    2015-11-01

    Chronic traumatic encephalopathy (CTE) is associated with repetitive mild traumatic brain injury (mTBI) in the context of contact and collision sports, but not all exposed individuals develop this condition. In addition, experiments in animal models in several laboratories have shown that non-transgenic mice do not develop tauopathy after exposure to repetitive mTBI schedules. It is thus reasonable to assume that genetic factors may play an etiological role in the development of CTE. More than 40 mutations in the tau gene are known to confer proneness to aggregation and are thought to cause neurodegenerative diseases including frontotemporal degeneration (FTD). Transgenic mice harboring these mutations can be used to ask the question whether repetitive mTBI can accelerate onset and course of tauopathy or worsen the outcomes of transgenic disease. In this study, we exposed mice harboring the tau P301S transgene associated with FTD to repetitive mTBI schedules by impact acceleration (IA) that we have previously characterized. We explored the progression of tauopathy in the retina and neocortex based on density of neuronal profiles loaded with tau pS422, a marker of advanced tau hyperphosphorylation. We found that the density of tau pS422 (+) retinal ganglion cells (RGCs) increased twenty fold with one mTBI hit, a little over fifty fold with four mTBI hits and sixty fold with 12 mTBI hits. The severity of mTBI burden (number of hits) was a significant factor in tauopathy outcome. On the other hand, we found no association between repetitive mTBI and density of pS422 (+) neuronal profiles in neocortex, a region that is not featured by significant TAI in our repetitive mTBI model. We observed similar, but less prominent, trends in tauopathy-prone transgenic mice harboring all 6 isoforms of wild-type human tau without mouse tau. Our findings indicate that repetitive mTBI accelerates tauopathy under diverse genetic conditions predisposing to tau aggregation and suggest a

  17. SU-E-T-538: Does Abdominal Compression Through Prone Patient Position Reduce Respiratory Motion in Lung Cancer Radiotherapy?

    SciTech Connect

    Catron, T; Rosu, M; Weiss, E

    2014-06-01

    Purpose: This study assesses the effect of physiological abdominal compression from prone positioning by comparing respiratory-induced tumor movements in supine and prone positions. Methods: 19 lung cancer patients underwent repeated supine and prone free-breathing 4DCT scans. The effect of patient position on motion magnitude was investigated for tumors, lymph nodes (9 cases), and subgroups of central (11 cases), peripheral (8 cases) and small peripheral tumors (5 cases), by evaluating the population average excursions, absolute and relative to a carina-point. Results: Absolute motion analysis: In prone, motion increased by ~20% for tumors and ~25% for lymph nodes. Central tumors moved more compared to peripheral tumors in both supine and prone (~22%, and ~4% respectively). Central tumors movement increased by ~12% in prone. For peripheral tumors the increase in prone position was ~25% (~40% and 29% changes on along RL and AP directions). Motion relative to carina-point analysis: Overall, tumor excursions relative to carina-point increased by ~17% in prone. Lymph node relative magnitudes were lower by ~4%. Likewise, the central tumors moved ~7% less in prone. The subgroup of peripheral tumors exhibited increased amplitudes by ~44%; the small peripheral tumors had even larger relative displacements in prone (~46%). Conclusion: Tumor and lymph node movement in the patient population from this study averaged to be higher in prone than in supine position. Results from carina analysis also suggest that peripheral tissues have more physiologic freedom of motility when placed in the prone position, regardless of size. From these observations we should continue to avoid prone positioning for all types of primary lung tumor, suggesting that patients should receive radiotherapy for primary lung cancer in supine position to minimize target tissue mobility during normal respiratory effort. Further investigation will include more patients with peripheral tumors to validate our

  18. Endoplasmic reticulum stress caused by aggregate-prone proteins containing homopolymeric amino acids.

    PubMed

    Uchio, Naohiro; Oma, Yoko; Toriumi, Kazuya; Sasagawa, Noboru; Tanida, Isei; Fujita, Eriko; Kouroku, Yoriko; Kuroda, Reiko; Momoi, Takashi; Ishiura, Shoichi

    2007-11-01

    Many human proteins have homopolymeric amino acid (HPAA) tracts, but their physiological functions or cellular effects are not well understood. Previously, we expressed 20 HPAAs in mammalian cells and showed characteristic intracellular localization, in that hydrophobic HPAAs aggregated strongly and caused high cytotoxicity in proportion to their hydrophobicity. In the present study, we investigated the cytotoxicity of these aggregate-prone hydrophobic HPAAs, assuming that the ubiquitin proteasome system is impaired in the same manner as other well-known aggregate-prone polyglutamine-containing proteins. Some highly hydrophobic HPAAs caused a deficiency in the ubiquitin proteasome system and excess endoplasmic reticulum stress, leading to apoptosis. These results indicate that the property of causing excess endoplasmic reticulum stress by proteasome impairment may contribute to the strong cytotoxicity of highly hydrophobic HPAAs, and proteasome impairment and the resulting excess endoplasmic reticulum stress is not a common cytotoxic effect of aggregate-prone proteins such as polyglutamine.

  19. Comparative Analysis of Decision Trees with Logistic Regression in Predicting Fault-Prone Classes

    NASA Astrophysics Data System (ADS)

    Singh, Yogesh; Takkar, Arvinder Kaur; Malhotra, Ruchika

    There are available metrics for predicting fault prone classes, which may help software organizations for planning and performing testing activities. This may be possible due to proper allocation of resources on fault prone parts of the design and code of the software. Hence, importance and usefulness of such metrics is understandable, but empirical validation of these metrics is always a great challenge. Decision Tree (DT) methods have been successfully applied for solving classification problems in many applications. This paper evaluates the capability of three DT methods and compares its performance with statistical method in predicting fault prone software classes using publicly available NASA data set. The results indicate that the prediction performance of DT is generally better than statistical model. However, similar types of studies are required to be carried out in order to establish the acceptability of the DT models.

  20. Deep vein thrombosis after spine operation in prone position with subclavian venous catheterization: a case report.

    PubMed

    Cho, Jae Kyung; Han, Jin Hee; Park, Sung Wook; Kim, Keon Sik

    2014-07-01

    We experienced a case of deep vein thrombosis after spine surgery in the prone position with a central venous catheter (CVC). Posterior lumbar interbody fusion was performed on a 73-year-old female patient who was diagnosed with spinal stenosis. Accordingly, in the operation room under general anesthesia, two-lumen CVC were inserted into the left subclavian vein. The surgery was performed in the prone position with a Wilson frame. On the next day, there was a sudden occurrence of severe edema in the patient's left arm. By ultrasonography and computed tomography scanning, extensive deep vein thrombosis was observed in the left subclavian vein. The existence of a factor affecting blood flow such as the prone position may increase the risk of thrombus formation. Therefore, careful perioperative evaluation should be implemented.

  1. Suicide proneness in college students: relationships with gender, procrastination, and achievement motivation.

    PubMed

    Klibert, Jeffrey; Langhinrichsen-Rohling, Jennifer; Luna, Amy; Robichaux, Michelle

    2011-08-01

    This study examined the relationships between 2 academic dispositions (i.e., procrastination and achievement motivation) and 2 indices of suicidal proneness in college women and men. The degree these 2 academic dispositions could predict unique variance in suicide proneness scores, above and beyond the influence of depression and self-esteem was also examined for each gender. Participants included 475 (336 women, 139 men) undergraduates from a southeastern university. For both genders, procrastination and achievement motivation were significantly correlated at the univarate level with the suicide proneness indices. However, for college women, but not men, procrastination significantly accounted for unique amounts of variance in both suicide indices above and beyond the influence of depression and self-esteem. Implications for suicide intervention efforts directed toward college women and men are offered.

  2. Registration of prone and supine colons in the presence of topological changes

    NASA Astrophysics Data System (ADS)

    Suh, Jung W.; Wyatt, Christopher L.

    2008-03-01

    CT colonography is a minimally-invasive screening technique for colorectal polyps in which X-ray CT images of the distended colon are acquired, usually in the prone and supine positions. Registration of segmented colons from both images will be useful for computer-assisted polyp detection. We have previously presented algorithms for registration of the prone and supine colon when both are well distended and there is a single connected lumen. However due to inadequate bowel preparation or peristalsis there may be collapsed segments in one or both of the colons resulting in a topological change in the images. Such changes make deformable registrations of the colons difficult, and at present there are no registration algorithms which can accommodate them. In this paper we present an algorithm which can perform volume registration of prone/supine colon images in the presence of a topological change.

  3. An introduction to acceleration mechanisms

    SciTech Connect

    Palmer, R.B.

    1987-05-01

    This paper discusses the acceleration of charged particles by electromagnetic fields, i.e., by fields that are produced by the motion of other charged particles driven by some power source. The mechanisms that are discussed include: Ponderamotive Forces, Acceleration, Plasma Beat Wave Acceleration, Inverse Free Electron Laser Acceleration, Inverse Cerenkov Acceleration, Gravity Acceleration, 2D Linac Acceleration and Conventional Iris Loaded Linac Structure Acceleration. (LSP)

  4. Evidence for higher tropical storm risks in Haiti due to increasing population density in hazard prone urban areas

    NASA Astrophysics Data System (ADS)

    Klose, Christian D.

    2011-10-01

    Since the 18th century, the Republic of Haiti has experienced numerous tropical cyclones. In 2011, the United Nations Global Assessment Report on Disaster Risk Reduction outlined that the worldwide physical exposure to natural hazards, which includes tropical storms and hurricanes in Haiti, increased by 192 per cent between 1970 and 2010. Now, it can be hypothesized that the increased physical exposure to cyclones that made landfall in Haiti has affected the country's development path. This study shows that tropical storm risks in Haiti increased due to more physical exposure of the population in urban areas rather than a higher cyclone frequency in the proximity of Hispaniola island. In fact, the population density accelerated since the second half of the 20th century in regions where historically more storms made landfall, such as in the departments Ouest, Artibonite, Nord and Nord-Ouest including Haiti's four largest cities: Port-au-Prince, Gonaïves, Cap-Haïtien and Port-de-Paix. Thus, urbanization in and migration into storm hazard prone areas could be considered as one of the major driving forces of Haiti's fragility.

  5. Otitis-Prone Children Produce Functional Antibodies to Pneumolysin and Pneumococcal Polysaccharides

    PubMed Central

    Wiertsema, Selma P.; Corscadden, Karli J.; Mateus, Tulia; Mullaney, Gemma L.; Zhang, Guicheng; Richmond, Peter C.; Thornton, Ruth B.

    2016-01-01

    ABSTRACT The pneumococcus is a major otitis media (OM) pathogen, but data are conflicting regarding whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titers to pneumococcal proteins and polysaccharides (vaccine and nonvaccine types); however, the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titer, is considered to be a better correlate of protection from pneumococcal disease. Therefore, we compared the capacities of antibodies from otitis-prone (cases) and healthy (controls) children to neutralize pneumolysin, the pneumococcal toxin currently in development as a vaccine antigen, and to opsonize pneumococcal vaccine and nonvaccine serotypes. A pneumolysin neutralization assay was conducted on cholesterol-depleted complement-inactivated sera from 165 cases and 61 controls. A multiplex opsonophagocytosis assay (MOPA) was conducted on sera from 20 cases and 20 controls. Neutralizing and opsonizing titers were calculated with antigen-specific IgG titers to determine antibody potency for pneumolysin, pneumococcal conjugate vaccine (PCV) polysaccharides, and non-PCV polysaccharides. There was no significant difference in antibody potencies between cases and controls for the antigens tested. Antipneumolysin neutralizing titers increased with the number of episodes of acute OM, but antibody potency did not. Pneumolysin antibody potency was lower in children colonized with pneumococci than in noncarriers, and this was significant for the otitis-prone group (P < 0.05). The production of functional antipneumococcal antibodies in otitis-prone children demonstrates that they respond to the current PCV and are likely to respond to pneumolysin-based vaccines as effectively as healthy children. PMID:28031178

  6. Protective effect of prone posture against hypergravity-induced arterial hypoxaemia in humans.

    PubMed

    Rohdin, M; Petersson, J; Mure, M; Glenny, R W; Lindahl, S G E; Linnarsson, D

    2003-04-15

    Patients with acute respiratory distress syndrome have increased lung tissue weight and therefore an increased hydrostatic pressure gradient down the lung. Also, they have a better arterial oxygenation in prone (face down) than in supine (face up) posture. We hypothesized that this effect of the direction of gravity also existed in healthy humans, when increased hydrostatic gradients were induced by hypergravity. Ten healthy subjects were studied in a human centrifuge while exposed to 1 or 5 G in anterio-posterior (supine) or posterio-anterior (prone) direction. We measured blood gases using remote-controlled sampling and gas exchange by mass spectrometry. Hypergravity led to marked impairments of arterial oxygenation in both postures and more so in supine posture. At 5 G, the arterial oxygen saturation was 84.6 +/- 1.2 % (mean +/- S.E.M.) in supine and 89.7 +/- 1.4 % in prone posture (P < 0.001 for supine vs. prone). Ventilation and alveolar PO2 were increased at 5 G and did not differ between postures. The alveolar-to-arterial PO2 difference increased at 5 G to 8.0 +/- 0.2 kPa and 6.6 +/- 0.3 kPa in supine and prone postures (P = 0.003). Arterial oxygenation was less impaired in prone during hypergravity due to a better-preserved alveolo-arterial oxygen transport. We speculate that mammals have developed a cardiopulmonary structure that favours function with the gravitational vector in the posterio-anterior direction.

  7. Follicle-stimulating hormone accelerates mouse oocyte development in vivo.

    PubMed

    Demeestere, Isabelle; Streiff, Agathe K; Suzuki, João; Al-Khabouri, Shaima; Mahrous, Enas; Tan, Seang Lin; Clarke, Hugh J

    2012-07-01

    During folliculogenesis, oocytes grow and acquire developmental competence in a mutually dependent relationship with their adjacent somatic cells. Follicle-stimulating hormone (FSH) plays an essential and well-established role in the differentiation of somatic follicular cells, but its function in the development of the oocyte has still not been elucidated. We report here that oocytes of Fshb(-/-) mice, which cannot produce FSH, grow at the same rate and reach the same size as those of wild-type mice. Consistent with this observation, the granulosa cells of Fshb(-/-) mice express the normal quantity of mRNA encoding Kit ligand, which has been implicated in oocyte growth. Oocytes of Fshb(-/-) mice also accumulate normal quantities of cyclin B1 and CDK1 proteins and mitochondrial DNA. Moreover, they acquire the ability to complete meiotic maturation in vitro and undergo transition from non-surrounded nucleolus to surrounded nucleolus. However, these events of late oocyte development are significantly delayed. Following in vitro maturation and fertilization, only a small number of embryos derived from oocytes of Fshb(-/-) mice reach the blastocyst stage. Administration of equine chorionic gonadotropin, which provides FSH activity, 48 h before in vitro maturation increases the number of blastocysts obtained subsequently. These results indicate that FSH is not absolutely required for oocyte development in vivo but that this process occurs more rapidly in its presence. We suggest that FSH may coordinate the development of the germline and somatic compartments of the follicle, ensuring that ovulation releases a developmentally competent egg.

  8. Comparison of Acute and Late Toxicity of Two Regimens of 3- and 5-Week Concomitant Boost Prone IMRT to Standard 6-Week Breast Radiotherapy

    PubMed Central

    Raza, Shahzad; Lymberis, Stella C.; Ciervide, Raquel; Axelrod, Deborah; Fenton-Kerimian, Maria; Magnolfi, Chiara; Rosenstein, Barry; DeWyngaert, J. Keith; Formenti, Silvia C.

    2012-01-01

    Purpose: Limited information is available comparing toxicity of accelerated radiotherapy (RT) to that of standard fractionation RT for early stage breast cancer. We report early and late toxicities of two prone regimens of accelerated intensity-modulated radiation therapy (IMRT) with a concomitant boost (CB) to the tumor bed delivered over 3 or 5 weeks as compared to standard 6 week RT with a sequential electron boost. Methods: From 2/2003 to 12/2007, 169 consecutive patients with Stage I–II breast cancer were offered the choice to undergo prone RT with either: a 6-week standard RT regimen of 46 Gy/23 fractions (fx) to the whole breast (WB), followed by a14 Gy sequential boost (SB) to the tumor bed (6wSB), a 5-week regimen of 50 Gy to WB with an IMRT CB of 6.25 Gy in 25 fx (5wCB); or a 3-week protocol of 40.5 Gy to WB with an IMRT CB of 7.5 Gy in 15 fx (3wCB). These regimens were estimated as biologically equivalent, based on alpha/beta = 4 for tumor control. Toxicities were reported using RTOG and LENT/SOMA scoring. Results: 51/169 patients chose standard 6wSB, 28 selected 5wCB, and 90 enrolled in 3wCB protocol. Maximum acute toxicity was Grade 3 dermatitis in 4% of the patients in the 6wSB compared 1% in 3wCB. In general, acute complications (breast pain, fatigue, and dermatitis) were significantly less in the 3wCB than in the other schedules (P < 0.05). With a median follow-up of 61 months, the only Grade 3 late toxicity was telangiectasia in two patients: one in 3wCB and one in 5wCB group. Notably, fibrosis was comparable among the three groups (P = NS). Conclusion: These preliminary data suggest that accelerated regimens of breast RT over 3 or 5 weeks in the prone position, with an IMRT tumor bed CB, result in comparable late toxicity to standard fractionation with a sequential tumor boost delivered over 6 weeks. As predicted by radiobiological modeling the shorter regimen was associated with less acute effects. PMID:22649788

  9. Schooling in Times of Acceleration

    ERIC Educational Resources Information Center

    Buddeberg, Magdalena; Hornberg, Sabine

    2017-01-01

    Modern societies are characterised by forms of acceleration, which influence social processes. Sociologist Hartmut Rosa has systematised temporal structures by focusing on three categories of social acceleration: technical acceleration, acceleration of social change, and acceleration of the pace of life. All three processes of acceleration are…

  10. Predicting Fault Prone Modules by the Dempster-Shafer Belief Networks

    PubMed Central

    Guo, Lan; Cukic, Bojan; Singh, Harshinder

    2015-01-01

    This paper describes a novel methodology for predicting fault prone modules. The methodology is based on Dempster-Shafer (D-S) belief networks. Our approach consists of three steps: First, building the Dempster-Shafer network by the induction algorithm; Second, selecting the predictors (attributes) by the logistic procedure; Third, feeding the predictors describing the modules of the current project into the inducted Dempster-Shafer network and identifying fault prone modules. We applied this methodology to a NASA dataset. The prediction accuracy of our methodology is higher than that achieved by logistic regression or discriminant analysis on the same dataset. PMID:26120284

  11. [Ventilation in prone decubitus in a patient with respiratory distress during heart surgery].

    PubMed

    Rama-Maceiras, P; Duro, J; Figueira-Moure, A; Rey-Rilo, T; Toral, A; Rodríguez-Rodríguez, A

    1999-02-01

    Acute respiratory failure and adult respiratory distress syndrome are serious complications after heart surgery and are associated with a high mortality rate. We report the case of a 50-year-old man who developed severe respiratory distress after heart surgery with extracorporeal circulation and for whom oxygenation was possible with ventilation in prone decubitus position only after other therapeutic measured had failed. The physiological bases of ventilation in prone decubitus position, as well as the indications and contraindications of the technique are discussed. Early treatment, which is fundamental for managing these patients, facilitates a favorable outcome as is illustrated by the case we report.

  12. Uniformly accelerated black holes

    NASA Astrophysics Data System (ADS)

    Letelier, Patricio S.; Oliveira, Samuel R.

    2001-09-01

    The static and stationary C metric are examined in a generic framework and their interpretations studied in some detail, especially those with two event horizons, one for the black hole and another for the acceleration. We find that (i) the spacetime of an accelerated static black hole is plagued by either conical singularities or a lack of smoothness and compactness of the black hole horizon, (ii) by using standard black hole thermodynamics we show that accelerated black holes have a higher Hawking temperature than Unruh temperature of the accelerated frame, and (iii) the usual upper bound on the product of the mass and acceleration parameters (<1/27) is just a coordinate artifact. The main results are extended to accelerated rotating black holes with no significant changes.

  13. The Dielectric Wall Accelerator

    SciTech Connect

    Caporaso, George J.; Chen, Yu-Jiuan; Sampayan, Stephen E.

    2009-01-01

    The Dielectric Wall Accelerator (DWA), a class of induction accelerators, employs a novel insulating beam tube to impress a longitudinal electric field on a bunch of charged particles. The surface flashover characteristics of this tube may permit the attainment of accelerating gradients on the order of 100 MV/m for accelerating pulses on the order of a nanosecond in duration. A virtual traveling wave of excitation along the tube is produced at any desired speed by controlling the timing of pulse generating modules that supply a tangential electric field to the tube wall. Because of the ability to control the speed of this virtual wave, the accelerator is capable of handling any charge to mass ratio particle; hence it can be used for electrons, protons and any ion. The accelerator architectures, key technologies and development challenges will be described.

  14. Optically pulsed electron accelerator

    DOEpatents

    Fraser, J.S.; Sheffield, R.L.

    1985-05-20

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radiofrequency-powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  15. Optically pulsed electron accelerator

    DOEpatents

    Fraser, John S.; Sheffield, Richard L.

    1987-01-01

    An optically pulsed electron accelerator can be used as an injector for a free electron laser and comprises a pulsed light source, such as a laser, for providing discrete incident light pulses. A photoemissive electron source emits electron bursts having the same duration as the incident light pulses when impinged upon by same. The photoemissive electron source is located on an inside wall of a radio frequency powered accelerator cell which accelerates the electron burst emitted by the photoemissive electron source.

  16. ACCELERATION RESPONSIVE SWITCH

    DOEpatents

    Chabrek, A.F.; Maxwell, R.L.

    1963-07-01

    An acceleration-responsive device with dual channel capabilities whereby a first circuit is actuated upon attainment of a predetermined maximum acceleration level and when the acceleration drops to a predetermined minimum acceleriltion level another circuit is actuated is described. A fluid-damped sensing mass slidably mounted in a relatively frictionless manner on a shaft through the intermediation of a ball bushing and biased by an adjustable compression spring provides inertially operated means for actuating the circuits. (AEC)

  17. The foxhole accelerating structure

    SciTech Connect

    Fernow, R.C.; Claus, J.

    1992-07-17

    This report examines some properties of a new type of open accelerating structure. It consists of a series of rectangular cavities, which we call foxholes, joined by a beam channel. The power for accelerating the particles comes from an external radiation source and enters the cavities through their open upper surfaces. Analytic and computer calculations are presented showing that the foxhole is a suitable structure for accelerating relativistic electrons.

  18. Particle acceleration in flares

    NASA Technical Reports Server (NTRS)

    Benz, Arnold O.; Kosugi, Takeo; Aschwanden, Markus J.; Benka, Steve G.; Chupp, Edward L.; Enome, Shinzo; Garcia, Howard; Holman, Gordon D.; Kurt, Victoria G.; Sakao, Taro

    1994-01-01

    Particle acceleration is intrinsic to the primary energy release in the impulsive phase of solar flares, and we cannot understand flares without understanding acceleration. New observations in soft and hard X-rays, gamma-rays and coherent radio emissions are presented, suggesting flare fragmentation in time and space. X-ray and radio measurements exhibit at least five different time scales in flares. In addition, some new observations of delayed acceleration signatures are also presented. The theory of acceleration by parallel electric fields is used to model the spectral shape and evolution of hard X-rays. The possibility of the appearance of double layers is further investigated.

  19. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-01-01

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  20. Charged particle accelerator grating

    DOEpatents

    Palmer, Robert B.

    1986-09-02

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams into the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  1. Accelerator-based BNCT.

    PubMed

    Kreiner, A J; Baldo, M; Bergueiro, J R; Cartelli, D; Castell, W; Thatar Vento, V; Gomez Asoia, J; Mercuri, D; Padulo, J; Suarez Sandin, J C; Erhardt, J; Kesque, J M; Valda, A A; Debray, M E; Somacal, H R; Igarzabal, M; Minsky, D M; Herrera, M S; Capoulat, M E; Gonzalez, S J; del Grosso, M F; Gagetti, L; Suarez Anzorena, M; Gun, M; Carranza, O

    2014-06-01

    The activity in accelerator development for accelerator-based BNCT (AB-BNCT) both worldwide and in Argentina is described. Projects in Russia, UK, Italy, Japan, Israel, and Argentina to develop AB-BNCT around different types of accelerators are briefly presented. In particular, the present status and recent progress of the Argentine project will be reviewed. The topics will cover: intense ion sources, accelerator tubes, transport of intense beams, beam diagnostics, the (9)Be(d,n) reaction as a possible neutron source, Beam Shaping Assemblies (BSA), a treatment room, and treatment planning in realistic cases.

  2. High Gradient Accelerator Research

    SciTech Connect

    Temkin, Richard

    2016-07-12

    The goal of the MIT program of research on high gradient acceleration is the development of advanced acceleration concepts that lead to a practical and affordable next generation linear collider at the TeV energy level. Other applications, which are more near-term, include accelerators for materials processing; medicine; defense; mining; security; and inspection. The specific goals of the MIT program are: • Pioneering theoretical research on advanced structures for high gradient acceleration, including photonic structures and metamaterial structures; evaluation of the wakefields in these advanced structures • Experimental research to demonstrate the properties of advanced structures both in low-power microwave cold test and high-power, high-gradient test at megawatt power levels • Experimental research on microwave breakdown at high gradient including studies of breakdown phenomena induced by RF electric fields and RF magnetic fields; development of new diagnostics of the breakdown process • Theoretical research on the physics and engineering features of RF vacuum breakdown • Maintaining and improving the Haimson / MIT 17 GHz accelerator, the highest frequency operational accelerator in the world, a unique facility for accelerator research • Providing the Haimson / MIT 17 GHz accelerator facility as a facility for outside users • Active participation in the US DOE program of High Gradient Collaboration, including joint work with SLAC and with Los Alamos National Laboratory; participation of MIT students in research at the national laboratories • Training the next generation of Ph. D. students in the field of accelerator physics.

  3. FFAGS for rapid acceleration

    SciTech Connect

    Carol J. Johnstone and Shane Koscielniak

    2002-09-30

    When large transverse and longitudinal emittances are to be transported through a circular machine, extremely rapid acceleration holds the advantage that the beam becomes immune to nonlinear resonances because there is insufficient time for amplitudes to build up. Uncooled muon beams exhibit large emittances and require fast acceleration to avoid decay losses and would benefit from this style of acceleration. The approach here employs a fixed-field alternating gradient or FFAG magnet structure and a fixed frequency acceleration system. Acceptance is enhanced by the use only of linear lattice elements, and fixed-frequency rf enables the use of cavities with large shunt resistance and quality factor.

  4. Acceleration of polarized protons in circular accelerators

    SciTech Connect

    Courant, E.D.; Ruth, R.D.

    1980-09-12

    The theory of depolarization in circular accelerators is presented. The spin equation is first expressed in terms of the particle orbit and then converted to the equivalent spinor equation. The spinor equation is then solved for three different situations: (1) a beam on a flat top near a resonance, (2) uniform acceleration through an isolated resonance, and (3) a model of a fast resonance jump. Finally, the depolarization coefficient, epsilon, is calculated in terms of properties of the particle orbit and the results are applied to a calculation of depolarization in the AGS.

  5. A novel POLH mutation causes XP-V disease and XP-V tumor proneness may involve imbalance of numerous DNA polymerases

    PubMed Central

    GUO, JIA; ZHOU, GUILAN; ZHANG, WENFENG; SONG, YALING; BIAN, ZHUAN

    2013-01-01

    Xeroderma pigmentosum variant (XP-V) is a subtype of xeroderma pigmentosum (XP) disease with typical pigmentation and types of cancer in the oral maxillofacial and other sun-exposed regions. Few factors of tumor proneness in XP-V have been completely elucidated with the exception of the POLH [which encodes DNA polymerase η (pol η)] mutation. The aim of the present study was to identify the POLH mutation in an XP-V patient and to explore the roles of specific additional polymerases in XP-V tumor proneness. The POLH gene was sequenced in the patient and the expression of pol η, ι, κ, θ and ζ was tested in XP-V tumor cells and cell lines, as well as in HeLa cells with POLH knockdown. The results revealed a novel, large homozygous deletion of POLH (del exon 5–9) in the patient. Lower expression of pol κ, θ and ζ were observed in the XP-V cells and similar changes were observed in HeLa cells with POLH knockdown. Consistent with XP-V tumor cells, following UV irradiation, the expression of pol κ and θ presented was significantly increased in the XP-V cell lines compared with that in the normal control cells. The unusual expression of other polymerases, besides pol η, identified in the present study indicated that these polymerases may also be key in XP-V cells genetic instability, which accelerates tumor formation. PMID:24260050

  6. Scaling FFAG accelerator for muon acceleration

    SciTech Connect

    Lagrange, JB.; Planche, T.; Mori, Y.

    2011-10-06

    Recent developments in scaling fixed field alternating gradient (FFAG) accelerators have opened new ways for lattice design, with straight sections, and insertions like dispersion suppressors. Such principles and matching issues are detailed in this paper. An application of these new concepts is presented to overcome problems in the PRISM project.

  7. Scaling FFAG accelerator for muon acceleration

    NASA Astrophysics Data System (ADS)

    Lagrange, JB.; Planche, T.; Mori, Y.

    2011-10-01

    Recent developments in scaling fixed field alternating gradient (FFAG) accelerators have opened new ways for lattice design, with straight sections, and insertions like dispersion suppressors. Such principles and matching issues are detailed in this paper. An application of these new concepts is presented to overcome problems in the PRISM project.

  8. Angular velocities, angular accelerations, and coriolis accelerations

    NASA Technical Reports Server (NTRS)

    Graybiel, A.

    1975-01-01

    Weightlessness, rotating environment, and mathematical analysis of Coriolis acceleration is described for man's biological effective force environments. Effects on the vestibular system are summarized, including the end organs, functional neurology, and input-output relations. Ground-based studies in preparation for space missions are examined, including functional tests, provocative tests, adaptive capacity tests, simulation studies, and antimotion sickness.

  9. Supine or prone position for mini-PNL procedure: does it matter.

    PubMed

    Tokatlı, Zafer; Gokce, Mehmet Ilker; Süer, Evren; Sağlam, Remzi

    2015-06-01

    In this study it is aimed to compare the success and complication rates of mini-PNL procedure in supine and prone positions. In this retrospective study data of 180 patients treated with MPNL either in supine (n = 54) or prone (n = 126) positions between May 2009 and August 2014 was investigated. Success was defined as no visible stones >2 mm. Perioperative complications were classified using the modified Clavien system. Groups were compared with Chi square test or Student t test and for statistical significance p value of 0.05 was accepted. Mean age of the population was 42.5 ± 8.2 years and mean stone size was 23.9 ± 4.1 mm. The two groups were similar with regard to demographic characteristics and stone related characteristics except the ASA status. Success rates of the supine and prone groups were 85.1 and 87.3%, respectively (p = 0.701). No statistically significant differences in terms of complications were observed. Mean operative time was the only parameter different between the two groups (55 vs 82 min, p = 0.001). Supine position for PNL seems to be promising and the complication and success rates are shown to be similar to the prone position with MPNL technique. The only significant benefit of this technique is shorter operative time.

  10. Change in trunk muscle activities with prone bridge exercise in patients with chronic low back pain

    PubMed Central

    Kong, Yong-soo; Park, Seol; Kweon, Mi-Gyong; Park, Ji-won

    2016-01-01

    [Purpose] The aim of this study was to determine the effect of three different bridge exercises on internal oblique, external oblique, transverse abdominis, and erector spinae activities. [Subjects and Methods] Forty-five subjects with chronic low back pain participated in this study. The training outcome was evaluated with three different testing methods: supine bridge exercise, supine bridge on Swiss ball exercise, and prone bridge exercise. The activities of the transverse abdominis, internal oblique, external oblique, and erector spinae were measured using surface electromyography. [Results] There were significant differences in the internal oblique, external oblique, and erector spinae according to the three kinds of bridging exercises. The internal oblique, external oblique and transverse abdominis activities were highest in the prone bridge exercise, followed by those in the supine bridge on Swiss ball exercise, and supine bridge exercises. The activity of erector spine was highest in the supine bridge on Swiss ball exercise followed by the supine bridge exercise and prone bridge exercise. [Conclusion] These results suggest that prone bridge exercise is more effective than conventional supine bridge exercise and supine bridge on Swiss ball in increasing trunk muscle activity of chronic low back pain patients. PMID:26957771

  11. 44 CFR 60.3 - Flood plain management criteria for flood-prone areas.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Flood plain management criteria for flood-prone areas. 60.3 Section 60.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood...

  12. 44 CFR 60.3 - Flood plain management criteria for flood-prone areas.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Flood plain management criteria for flood-prone areas. 60.3 Section 60.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood...

  13. 44 CFR 60.3 - Flood plain management criteria for flood-prone areas.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Flood plain management criteria for flood-prone areas. 60.3 Section 60.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood...

  14. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing...

  15. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing...

  16. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing...

  17. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing...

  18. 44 CFR 60.3 - Flood plain management criteria for flood-prone areas.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Flood plain management criteria for flood-prone areas. 60.3 Section 60.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood...

  19. 44 CFR 60.24 - Planning considerations for flood-related erosion-prone areas.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... flood-related erosion-prone areas. 60.24 Section 60.24 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program CRITERIA FOR LAND MANAGEMENT AND USE Additional Considerations in Managing...

  20. 44 CFR 60.3 - Flood plain management criteria for flood-prone areas.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Flood plain management criteria for flood-prone areas. 60.3 Section 60.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood...

  1. A Modified Obesity Proneness Model Predicts Adolescent Weight Concerns and Inability to Self-Regulate Eating

    ERIC Educational Resources Information Center

    Nickelson, Jen; Bryant, Carol A.; McDermott, Robert J.; Buhi, Eric R.; DeBate, Rita D.

    2012-01-01

    Background: The prevalence of obesity among high school students has risen in recent decades. Many high school students report trying to lose weight and some engage in disordered eating to do so. The obesity proneness model suggests that parents may influence their offspring's development of disordered eating. This study examined the viability of…

  2. Binge eating proneness emerges during puberty in female rats: a longitudinal study.

    PubMed

    Klump, Kelly L; Suisman, Jessica L; Culbert, Kristen M; Kashy, Deborah A; Sisk, Cheryl L

    2011-11-01

    Puberty is a critical risk period for binge eating and eating disorders characterized by binge eating. Previous research focused almost entirely on psychosocial risk factors during puberty to the relative exclusion of biological influences. The current study addressed this gap by examining the emergence of binge eating during puberty in a rat model. We predicted that there would be minimal differences in binge eating proneness during pre-early puberty, but significant differences would emerge during puberty. Two independent samples of female Sprague-Dawley rats (n = 30 and n = 36) were followed longitudinally across pre-early puberty, mid-late puberty, and adulthood. Binge eating proneness was defined using the binge eating resistant (BER)/binge eating prone (BEP) model of binge eating that identifies BER and BEP rats in adulthood. Across two samples of rats, binge eating proneness emerged during puberty. Mixed linear models showed little difference in palatable food intake between BER and BEP rats during pre-early puberty, but significant group differences emerged during mid-late puberty and adulthood. Group differences could not be accounted for by changes in nonpalatable food intake or body weight. Similar to patterns in humans, individual differences in binge eating emerge during puberty in female rats. These findings provide strong confirming evidence for the importance of biological risk factors in developmental trajectories of binge eating risk across adolescence.

  3. "Deviance Proneness" and Adolescent Smoking 1980 versus 2001: Has There Been a "Hardening" of Adolescent Smoking?

    ERIC Educational Resources Information Center

    Chassin, Laurie; Presson, Clark; Morgan-Lopez, Antonio; Sherman, Steven J.

    2007-01-01

    In a midwestern community sample, we tested for evidence of "hardening" of adolescent cigarette smoking between 1980 and 2001 by comparing adolescent smokers and nonsmokers at these two times on measures indicative of "deviance proneness" in Jessor and Jessor's [Jessor, R., & Jessor, S. L. (1977). "Problem behavior and psychosocial development: A…

  4. Shame and Guilt-Proneness in Adolescents: Gene-Environment Interactions

    PubMed Central

    Szentágotai-Tătar, Aurora; Chiș, Adina; Vulturar, Romana; Dobrean, Anca; Cândea, Diana Mirela; Miu, Andrei C.

    2015-01-01

    Rooted in people’s preoccupation with how they are perceived and evaluated, shame and guilt are self-conscious emotions that play adaptive roles in social behavior, but can also contribute to psychopathology when dysregulated. Shame and guilt-proneness develop during childhood and adolescence, and are influenced by genetic and environmental factors that are little known to date. This study investigated the effects of early traumatic events and functional polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and the serotonin transporter gene promoter (5-HTTLPR) on shame and guilt in adolescents. A sample of N = 271 healthy adolescents between 14 and 17 years of age filled in measures of early traumatic events and proneness to shame and guilt, and were genotyped for the BDNF Val66Met and 5-HTTLPR polymorphisms. Results of moderator analyses indicated that trauma intensity was positively associated with guilt-proneness only in carriers of the low-expressing Met allele of BDNF Val66Met. This is the first study that identifies a gene-environment interaction that significantly contributes to guilt proneness in adolescents, with potential implications for developmental psychopathology. PMID:26230319

  5. Do Guilt- and Shame-Proneness Differentially Predict Prosocial, Aggressive, and Withdrawn Behaviors during Early Adolescence?

    ERIC Educational Resources Information Center

    Roos, Sanna; Hodges, Ernest V. E.; Salmivalli, Christina

    2014-01-01

    In this short-term longitudinal study, we systematically examined the distinctiveness of guilt- and shame-proneness in early adolescents (N = 395, mean age = 11.8 years) in terms of differential relations with peer reported prosocial behavior, withdrawal, and aggression. Results from structural equation modeling indicated that guilt-proneness…

  6. The Coronary-Prone Behavior Pattern and Trait Anxiety: Evidence for Discriminant Validity.

    ERIC Educational Resources Information Center

    Nielson, Warren R.; Dobson, Keith S.

    1980-01-01

    Supports the discriminant validity of the Coronary-Prone Behavior Pattern, as assessed by the Jenkins Activity Survey, in relation to trait anxiety. Future research should include measures of trait anxiety to collaborate findings in a laboratory setting. (Author/JAC)

  7. Female Coronary-Prone Behaviors: Relationship to Alpha and Self-Concept.

    ERIC Educational Resources Information Center

    Comer, David W.; And Others

    Researchers have been working toward isolating a set of psychological risk factors that would reliably predict coronary problems. This coronary-prone behavior pattern, Type A, is characterized by extremes of competitiveness, striving for achievement, impatience, and hostility. Differences were examined between 20 Type A and 20 Type B…

  8. 44 CFR 60.23 - Planning considerations for mudslide (i.e., mudflow)-prone areas.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Planning considerations for mudslide (i.e., mudflow)-prone areas. 60.23 Section 60.23 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National...

  9. [Methodic approaches to determining the level of occupational fitness in jobs prone to trauma].

    PubMed

    Iushkova, O I; Matiukhin, V V; Poroshenko, A S; Iampol'skaia, E G

    2006-01-01

    The article deals with main methods to evaluate functional state of various body systems and with the methods-based criteria of occupational fitness for miscellaneous activities. Examination of 11 types of jobs prone to trauma helped to specify integral parameter for occupational selection.

  10. Induction linear accelerators

    NASA Astrophysics Data System (ADS)

    Birx, Daniel

    1992-03-01

    Among the family of particle accelerators, the Induction Linear Accelerator is the best suited for the acceleration of high current electron beams. Because the electromagnetic radiation used to accelerate the electron beam is not stored in the cavities but is supplied by transmission lines during the beam pulse it is possible to utilize very low Q (typically<10) structures and very large beam pipes. This combination increases the beam breakup limited maximum currents to of order kiloamperes. The micropulse lengths of these machines are measured in 10's of nanoseconds and duty factors as high as 10-4 have been achieved. Until recently the major problem with these machines has been associated with the pulse power drive. Beam currents of kiloamperes and accelerating potentials of megavolts require peak power drives of gigawatts since no energy is stored in the structure. The marriage of liner accelerator technology and nonlinear magnetic compressors has produced some unique capabilities. It now appears possible to produce electron beams with average currents measured in amperes, peak currents in kiloamperes and gradients exceeding 1 MeV/meter, with power efficiencies approaching 50%. The nonlinear magnetic compression technology has replaced the spark gap drivers used on earlier accelerators with state-of-the-art all-solid-state SCR commutated compression chains. The reliability of these machines is now approaching 1010 shot MTBF. In the following paper we will briefly review the historical development of induction linear accelerators and then discuss the design considerations.

  11. Accelerator Science: Why RF?

    SciTech Connect

    Lincoln, Don

    2016-12-21

    Particle accelerators can fire beams of subatomic particles at near the speed of light. The accelerating force is generated using radio frequency technology and a whole lot of interesting features. In this video, Fermilab’s Dr. Don Lincoln explains how it all works.

  12. Particle Acceleration in Jets

    NASA Technical Reports Server (NTRS)

    Nishikawa, Ken-Ichi

    2005-01-01

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks, e.g., active galactic nuclei (AGNs), gamma ray burst (GRBs), and Galactic microquasar systems usually have power-law emission spectra. Fermi acceleration is the mechanism usually assumed for the acceleration of particles in astrophysical environments.

  13. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph; /Fermilab

    2010-07-01

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?

  14. Accelerators (3/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  15. Diagnostics for induction accelerators

    SciTech Connect

    Fessenden, T.J.

    1996-04-01

    The induction accelerator was conceived by N. C. Christofilos and first realized as the Astron accelerator that operated at LLNL from the early 1960`s to the end of 1975. This accelerator generated electron beams at energies near 6 MeV with typical currents of 600 Amperes in 400 ns pulses. The Advanced Test Accelerator (ATA) built at Livermore`s Site 300 produced 10,000 Ampere beams with pulse widths of 70 ns at energies approaching 50 MeV. Several other electron and ion induction accelerators have been fabricated at LLNL and LBNL. This paper reviews the principal diagnostics developed through efforts by scientists at both laboratories for measuring the current, position, energy, and emittance of beams generated by these high current, short pulse accelerators. Many of these diagnostics are closely related to those developed for other accelerators. However, the very fast and intense current pulses often require special diagnostic techniques and considerations. The physics and design of the more unique diagnostics developed for electron induction accelerators are presented and discussed in detail.

  16. Accelerators (4/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  17. Measuring Model Rocket Acceleration.

    ERIC Educational Resources Information Center

    Jenkins, Randy A.

    1993-01-01

    Presents an experiment that measures the acceleration and velocity of a model rocket. Lift-off information is transmitted to a computer that creates a graph of the velocity. Discusses the analysis of the computer-generated data and differences between calculated and experimental velocity and acceleration of several rocket types. (MDH)

  18. Microscale acceleration history discriminators

    DOEpatents

    Polosky, Marc A.; Plummer, David W.

    2002-01-01

    A new class of micromechanical acceleration history discriminators is claimed. These discriminators allow the precise differentiation of a wide range of acceleration-time histories, thereby allowing adaptive events to be triggered in response to the severity (or lack thereof) of an external environment. Such devices have applications in airbag activation, and other safety and surety applications.

  19. Accelerators (5/5)

    ScienceCinema

    None

    2016-07-12

    1a) Introduction and motivation 1b) History and accelerator types 2) Transverse beam dynamics 3a) Longitudinal beam dynamics 3b) Figure of merit of a synchrotron/collider 3c) Beam control 4) Main limiting factors 5) Technical challenges Prerequisite knowledge: Previous knowledge of accelerators is not required.

  20. Accelerators Beyond The Tevatron?

    SciTech Connect

    Lach, Joseph

    2010-07-29

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?.

  1. Accelerators, Beams And Physical Review Special Topics - Accelerators And Beams

    SciTech Connect

    Siemann, R.H.; /SLAC

    2011-10-24

    Accelerator science and technology have evolved as accelerators became larger and important to a broad range of science. Physical Review Special Topics - Accelerators and Beams was established to serve the accelerator community as a timely, widely circulated, international journal covering the full breadth of accelerators and beams. The history of the journal and the innovations associated with it are reviewed.

  2. Is the supine position superior to the prone position for percutaneous nephrolithotomy (PCNL)?

    PubMed

    Zhang, Xiaohua; Xia, Leilei; Xu, Tianyuan; Wang, Xianjin; Zhong, Shan; Shen, Zhoujun

    2014-02-01

    The objective of this study is to update the two previous meta-analyses in order to evaluate the efficacy and safety of percutaneous nephrolithotomy (PCNL) for patients in the prone position versus supine position. An electronic database search of MEDLINE, EMBASE, google scholar, and the Cochrane library was performed up to June, 2013. All studies comparing prone with supine position for PCNL were included. The outcome measures were stone-free rate, operative time, complication and hospital stay. Two randomized controlled trials (RCTs) and 7 non-RCTs, including 6,413 patients (4,956 patients in the prone position group and 1,457 patients in the supine position group), met the inclusion criteria. Meta-analysis of extractable data showed that PCNL in the supine position was associated with a significantly shorter operative time (WMD: 21.7; 95% CI 2.46-40.94; p = 0.03) but lower stone-free rate (OR: 1.36; 95% CI 1.19-1.56; p < 0.0001) than PCNL in the prone position. There was no difference between the two positions regarding hospital stay (WMD = 0.05; 95% CI -0.16-0.25; p = 0.66) and complication rate (OR: 1.1; 95% CI 0.94-1.28; p = 0.24). In conclusion, the present study found different results from the two previous meta-analyses results regarding stone-free rate; PCNL in the supine position had a significantly lower stone-free rate than that in prone position.

  3. Error-prone ZW pairing and no evidence for meiotic sex chromosome inactivation in the chicken germ line.

    PubMed

    Guioli, Silvana; Lovell-Badge, Robin; Turner, James M A

    2012-01-01

    In the male mouse the X and Y chromosomes pair and recombine within the small pseudoautosomal region. Genes located on the unsynapsed segments of the X and Y are transcriptionally silenced at pachytene by Meiotic Sex Chromosome Inactivation (MSCI). The degree to which MSCI is conserved in other vertebrates is currently unclear. In the female chicken the ZW bivalent is thought to undergo a transient phase of full synapsis at pachytene, starting from the homologous ends and spreading through the heterologous regions. It has been proposed that the repair of the ZW DNA double-strand breaks (DSBs) is postponed until diplotene and that the ZW bivalent is subject to MSCI, which is independent of its synaptic status. Here we present a distinct model of meiotic pairing and silencing of the ZW pair during chicken oogenesis. We show that, in most oocytes, DNA DSB foci on the ZW are resolved by the end of pachytene and that the ZW desynapses in broad synchrony with the autosomes. We unexpectedly find that ZW pairing is highly error prone, with many oocytes failing to engage in ZW synapsis and crossover formation. Oocytes with unsynapsed Z and W chromosomes nevertheless progress to the diplotene stage, suggesting that a checkpoint does not operate during pachytene in the chicken germ line. Using a combination of epigenetic profiling and RNA-FISH analysis, we find no evidence for MSCI, associated with neither the asynaptic ZW, as described in mammals, nor the synaptic ZW. The lack of conservation of MSCI in the chicken reopens the debate about the evolution of MSCI and its driving forces.

  4. Purine receptor antagonist modulates serology and affective behaviors in lupus-prone mice: evidence of autoimmune-induced pain?

    PubMed Central

    Ballok, David A.; Sakic, Boris

    2008-01-01

    Neurologic and psychiatric (NP) manifestations are severe complications of systemic lupus erythematosus (SLE). As commonly seen in patients, spontaneous disease onset in the MRL/MpJ-Faslpr/ J (MRL-lpr) mouse model of NP-SLE is accompanied by increased autoantibodies, proinflammatorycytokines and behavioral dysfunction which precede neuroinflammation and structural brain lesions. The role of purinergic receptors in the regulation of immunity and behavior remains largely unexplored in the field of neuropsychiatry. To examine the possibility that purinoception is involved in the development of affective behaviors, the P2X purinoceptor antagonist, suramin, was administered to lupus-prone mice from 5 to 14 weeks of age. In addition to food and water measures, novel object and sucrose preference tests were performed to assess neophobic anxiety- and anhedonic-like behaviors. Enzyme-linked immunosorbant assays for anti-nuclear antibodies (ANA) and pro-inflammatory cytokines were employed in immunopathological analyses. Changes in dendritic morphology in the hippocampal CA1 region were examined by a Golgi impregnation method. Suramin significantly lowered serum ANA and prevented behavioral deficits, but did not prevent neuronal atrophy in MRL-lpr animals. In a new batch of asymptomatic mice, systemic administration of corticosterone was found to induce aberrations in CA1 dendrites, comparable to the “stress” of chronic disease. The precise mechanism(s) through which purine receptor inhibition exerted beneficial effects is not known. The present data supports the hypothesis that activation of the peripheral immune system induces nociceptive-related behavioral symptomatology which is attenuated by the analgesic effects of suramin. Hypercortisolemia may also initiate neuronal damage, and metabolic perturbations may underlie neuro-immuno-endocrine imbalances in MRL-lpr mice. PMID:18601998

  5. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    PubMed

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  6. Large electrostatic accelerators

    SciTech Connect

    Jones, C.M.

    1984-01-01

    The increasing importance of energetic heavy ion beams in the study of atomic physics, nuclear physics, and materials science has partially or wholly motivated the construction of a new generation of large electrostatic accelerators designed to operate at terminal potentials of 20 MV or above. In this paper, the author briefly discusses the status of these new accelerators and also discusses several recent technological advances which may be expected to further improve their performance. The paper is divided into four parts: (1) a discussion of the motivation for the construction of large electrostatic accelerators, (2) a description and discussion of several large electrostatic accelerators which have been recently completed or are under construction, (3) a description of several recent innovations which may be expected to improve the performance of large electrostatic accelerators in the future, and (4) a description of an innovative new large electrostatic accelerator whose construction is scheduled to begin next year. Due to time and space constraints, discussion is restricted to consideration of only tandem accelerators.

  7. Differences in innate immune response gene regulation in the middle ear of children who are otitis prone and in those not otitis prone

    PubMed Central

    Casey, Janet; Pichichero, Michael

    2016-01-01

    Objective: Acute otitis media (AOM) causes an inflammatory response in the middle ear. We assessed differences in innate immune responses involved in bacterial defense at onset of AOM in children who were stringently defined as otitis prone (sOP) and children not otitis prone (NOP). Study Design: Innate immune genes analysis from middle ear fluid (MEF) samples of children. Methods: Genes of toll-like receptors (TLR), nod-like and retinoic acid-inducible gene-I-like receptors, downstream effectors important for inflammation and apoptosis, including cytokines and chemokines, were studied from MEF samples by using a real-time polymerase chain reaction array. Protein levels of differentially regulated genes were measured by Luminex. Results: Gene expression in MEF among children who were sOP was significantly different in upregulation of interleukin 8, secretory leukocyte peptidase inhibitor, and chemokine (C-C motif) ligand 3, and in downregulation of interferon regulatory factor 7 and its related signaling molecules interferon alpha, Toll-like receptor adaptor molecule 2, chemokine (C-C motif) ligand 5, and mitogen-activated protein kinase 8 compared with children who were NOP. Differences in innate gene regulation were similar when AOM was caused by Streptococcus pneumoniae or nontypeable Haemophilus influenzae. Conclusion: Innate-immune response genes are differentially regulated in children who were sOP compared with children with NOP. PMID:28124644

  8. Evaluation of the anatomical parameters for normal tissue sparing in the prone position radiotherapy with small sized left breasts

    PubMed Central

    Kim, Hyunjung; Kim, Jinyoung

    2016-01-01

    Prone position radiotherapy for a small (< 750 cm3) breast is controversial because of the variable benefits for the irradiated heart volume. The objective anatomical parameters related with chest wall shape that can determine the heart dose sparing patients in the prone position. Twenty-one patients underwent CT-simulation in supine and prone position. Dose volume parameters were compared and the objective indexes such as the Haller index, anthropometric index, mid-sternum thickness, and central lung distance (CLD) were evaluated the relationship between the shape of the chest wall and irradiated normal tissue volume in prone position. The median breast volume was 440.10 cm3 (range, 151.5–727.41 cm3). There was no difference of breast target volume between supine and prone position (p = 0.178). The Haller index under 2.5 (p = 0.046), an anthropometric index over 0.05 (p = 0.007), and the CLD over 2 (p = 0.023) conferred a greater heart sparing effect in the prone position. In conclusions, the objective anatomical parameters related chest wall shape predict the decrease in irradiated heart volume in the prone position. Therefore, it is possible to screen for patients with a reduced heart volume irradiation among those with small breasts before applying prone position radiotherapy. PMID:27756882

  9. 77 FR 41881 - Safety Advisory 2012-03; Buckling-Prone Conditions in Continuous Welded Rail Track

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-16

    ... Federal Railroad Administration Safety Advisory 2012-03; Buckling-Prone Conditions in Continuous Welded... identify buckling-prone conditions. In an effort to heighten awareness of the potential consequences of an... railroads to be caused by the rail buckling under extreme heat conditions (commonly referred to as...

  10. Vacuum Beat Wave Accelerator

    NASA Astrophysics Data System (ADS)

    Moore, C. I.; Hafizi, B.; Ting, A.; Burris, H. R.; Sprangle, P.; Esarey, E.; Ganguly, A.; Hirshfield, J. L.

    1997-11-01

    The Vacuum Beat Wave Accelerator (VBWA) is a particle acceleration scheme which uses the non-linear ponderomotive beating of two different frequency laser beams to accelerate electrons. A proof-of-principle experiment to demonstrate the VBWA is underway at the Naval Research Laboratory (NRL). This experiment will use the beating of a 1054 nm and 527 nm laser pulse from the NRL T-cubed laser to generate the beat wave and a 4.5 MeV RF electron gun as the electron source. Simulation results and the experimental design will be presented. The suitability of using axicon or higher order Gaussian laser beams will also be discussed.

  11. Ion beam accelerator system

    NASA Technical Reports Server (NTRS)

    Aston, Graeme (Inventor)

    1984-01-01

    A system is described that combines geometrical and electrostatic focusing to provide high ion extraction efficiency and good focusing of an accelerated ion beam. The apparatus includes a pair of curved extraction grids (16, 18) with multiple pairs of aligned holes positioned to direct a group of beamlets (20) along converging paths. The extraction grids are closely spaced and maintained at a moderate potential to efficiently extract beamlets of ions and allow them to combine into a single beam (14). An accelerator electrode device (22) downstream from the extraction grids, is at a much lower potential than the grids to accelerate the combined beam.

  12. Ion beam accelerator system

    NASA Technical Reports Server (NTRS)

    Aston, G. (Inventor)

    1981-01-01

    A system is described that combines geometrical and electrostatic focusing to provide high ion extraction efficiency and good focusing of an accelerated ion beam. The apparatus includes a pair of curved extraction grids with multiple pairs of aligned holes positioned to direct a group of beamlets along converging paths. The extraction grids are closely spaced and maintained at a moderate potential to efficiently extract beamlets of ions and allow them to combine into a single beam. An accelerator electrode device downstream from the extraction grids is at a much lower potential than the grids to accelerate the combined beam. The application of the system to ion implantation is mentioned.

  13. Designing an Algorithm to Preserve Privacy for Medical Record Linkage With Error-Prone Data

    PubMed Central

    Pal, Doyel; Chen, Tingting; Khethavath, Praveen

    2014-01-01

    Background Linking medical records across different medical service providers is important to the enhancement of health care quality and public health surveillance. In records linkage, protecting the patients’ privacy is a primary requirement. In real-world health care databases, records may well contain errors due to various reasons such as typos. Linking the error-prone data and preserving data privacy at the same time are very difficult. Existing privacy preserving solutions for this problem are only restricted to textual data. Objective To enable different medical service providers to link their error-prone data in a private way, our aim was to provide a holistic solution by designing and developing a medical record linkage system for medical service providers. Methods To initiate a record linkage, one provider selects one of its collaborators in the Connection Management Module, chooses some attributes of the database to be matched, and establishes the connection with the collaborator after the negotiation. In the Data Matching Module, for error-free data, our solution offered two different choices for cryptographic schemes. For error-prone numerical data, we proposed a newly designed privacy preserving linking algorithm named the Error-Tolerant Linking Algorithm, that allows the error-prone data to be correctly matched if the distance between the two records is below a threshold. Results We designed and developed a comprehensive and user-friendly software system that provides privacy preserving record linkage functions for medical service providers, which meets the regulation of Health Insurance Portability and Accountability Act. It does not require a third party and it is secure in that neither entity can learn the records in the other’s database. Moreover, our novel Error-Tolerant Linking Algorithm implemented in this software can work well with error-prone numerical data. We theoretically proved the correctness and security of our Error

  14. Antioxidants accelerate lung cancer progression in mice.

    PubMed

    Sayin, Volkan I; Ibrahim, Mohamed X; Larsson, Erik; Nilsson, Jonas A; Lindahl, Per; Bergo, Martin O

    2014-01-29

    Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies. However, clinical trials have reported inconsistent results. We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF- and K-RAS-induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect. Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production.

  15. CLASHING BEAM PARTICLE ACCELERATOR

    DOEpatents

    Burleigh, R.J.

    1961-04-11

    A charged-particle accelerator of the proton synchrotron class having means for simultaneously accelerating two separate contra-rotating particle beams within a single annular magnet structure is reported. The magnet provides two concentric circular field regions of opposite magnetic polarity with one field region being of slightly less diameter than the other. The accelerator includes a deflector means straddling the two particle orbits and acting to collide the two particle beams after each has been accelerated to a desired energy. The deflector has the further property of returning particles which do not undergo collision to the regular orbits whereby the particles recirculate with the possibility of colliding upon subsequent passages through the deflector.

  16. Vibration control in accelerators

    SciTech Connect

    Montag, C.

    2011-01-01

    In the vast majority of accelerator applications, ground vibration amplitudes are well below tolerable magnet jitter amplitudes. In these cases, it is necessary and sufficient to design a rigid magnet support structure that does not amplify ground vibration. Since accelerator beam lines are typically installed at an elevation of 1-2m above ground level, special care has to be taken in order to avoid designing a support structure that acts like an inverted pendulum with a low resonance frequency, resulting in untolerable lateral vibration amplitudes of the accelerator components when excited by either ambient ground motion or vibration sources within the accelerator itself, such as cooling water pumps or helium flow in superconducting magnets. In cases where ground motion amplitudes already exceed the required jiter tolerances, for instance in future linear colliders, passive vibration damping or active stabilization may be considered.

  17. Dielectric assist accelerating structure

    NASA Astrophysics Data System (ADS)

    Satoh, D.; Yoshida, M.; Hayashizaki, N.

    2016-01-01

    A higher-order TM02 n mode accelerating structure is proposed based on a novel concept of dielectric loaded rf cavities. This accelerating structure consists of ultralow-loss dielectric cylinders and disks with irises which are periodically arranged in a metallic enclosure. Unlike conventional dielectric loaded accelerating structures, most of the rf power is stored in the vacuum space near the beam axis, leading to a significant reduction of the wall loss, much lower than that of conventional normal-conducting linac structures. This allows us to realize an extremely high quality factor and a very high shunt impedance at room temperature. A simulation of a 5 cell prototype design with an existing alumina ceramic indicates an unloaded quality factor of the accelerating mode over 120 000 and a shunt impedance exceeding 650 M Ω /m at room temperature.

  18. Wake field acceleration experiments

    SciTech Connect

    Simpson, J.D.

    1988-01-01

    Where and how will wake field acceleration devices find use for other than, possibly, accelerators for high energy physics. I don't know that this can be responsibly answered at this time. What I can do is describe some recent results from an ongoing experimental program at Argonne which support the idea that wake field techniques and devices are potentially important for future accelerators. Perhaps this will spawn expanded interest and even new ideas for the use of this new technology. The Argonne program, and in particular the Advanced Accelerator Test Facility (AATF), has been reported in several fairly recent papers and reports. But because this is a substantially new audience for the subject, I will include a brief review of the program and the facility before describing experiments. 10 refs., 7 figs.

  19. Accelerator on a Chip

    SciTech Connect

    England, Joel

    2014-06-30

    SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

  20. Charged particle accelerator grating

    DOEpatents

    Palmer, R.B.

    1985-09-09

    A readily disposable and replaceable accelerator grating for a relativistic particle accelerator is described. The grating is formed for a plurality of liquid droplets that are directed in precisely positioned jet streams to periodically dispose rows of droplets along the borders of a predetermined particle beam path. A plurality of lasers are used to direct laser beams onto the droplets, at predetermined angles, thereby to excite the droplets to support electromagnetic accelerating resonances on their surfaces. Those resonances operate to accelerate and focus particles moving along the beam path. As the droplets are distorted or destroyed by the incoming radiation, they are replaced at a predetermined frequency by other droplets supplied through the jet streams.

  1. HEAVY ION LINEAR ACCELERATOR

    DOEpatents

    Van Atta, C.M.; Beringer, R.; Smith, L.

    1959-01-01

    A linear accelerator of heavy ions is described. The basic contributions of the invention consist of a method and apparatus for obtaining high energy particles of an element with an increased charge-to-mass ratio. The method comprises the steps of ionizing the atoms of an element, accelerating the resultant ions to an energy substantially equal to one Mev per nucleon, stripping orbital electrons from the accelerated ions by passing the ions through a curtain of elemental vapor disposed transversely of the path of the ions to provide a second charge-to-mass ratio, and finally accelerating the resultant stripped ions to a final energy of at least ten Mev per nucleon.

  2. Principles of Induction Accelerators

    NASA Astrophysics Data System (ADS)

    Briggs*, Richard J.

    The basic concepts involved in induction accelerators are introduced in this chapter. The objective is to provide a foundation for the more detailed coverage of key technology elements and specific applications in the following chapters. A wide variety of induction accelerators are discussed in the following chapters, from the high current linear electron accelerator configurations that have been the main focus of the original developments, to circular configurations like the ion synchrotrons that are the subject of more recent research. The main focus in the present chapter is on the induction module containing the magnetic core that plays the role of a transformer in coupling the pulsed power from the modulator to the charged particle beam. This is the essential common element in all these induction accelerators, and an understanding of the basic processes involved in its operation is the main objective of this chapter. (See [1] for a useful and complementary presentation of the basic principles in induction linacs.)

  3. Accelerator on a Chip

    ScienceCinema

    England, Joel

    2016-07-12

    SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

  4. DIELECTRIC WALL ACCELERATOR TECHNOLOGY

    SciTech Connect

    Sampayan, S; Caporaso, G; Chen, Y; Harris, J; Hawkins, S; Holmes, C; Nelson, S; Poole, B; Rhodes, M; Sanders, D; Sullivan, J; Wang, L; Watson, J

    2007-10-18

    The dielectric wall accelerator (DWA) is a compact pulsed power device where the pulse forming lines, switching, and vacuum wall are integrated into a single compact geometry. For this effort, we initiated a extensive compact pulsed power development program and have pursued the study of switching (gas, oil, laser induced surface flashover and photoconductive), dielectrics (ceramics and nanoparticle composites), pulse forming line topologies (asymmetric and symmetric Blumleins and zero integral pulse forming lines), and multilayered vacuum insulator (HGI) technology. Finally, we fabricated an accelerator cell for test on ETAII (a 5.5 MeV, 2 kA, 70 ns pulsewidth electron beam accelerator). We review our past results and report on the progress of accelerator cell testing.

  5. Development of a syngeneic mouse model of epithelial ovarian cancer

    PubMed Central

    2010-01-01

    Background Most cases of ovarian cancer are epithelial in origin and diagnosed at advanced stage when the cancer is widely disseminated in the peritoneal cavity. The objective of this study was to establish an immunocompetent syngeneic mouse model of disseminated epithelial ovarian cancer (EOC) to facilitate laboratory-based studies of ovarian tumor biology and preclinical therapeutic strategies. Methods Individual lines of TgMISIIR-TAg transgenic mice were phenotypically characterized and backcrossed to inbred C57BL/6 mice. In addition to a previously described line of EOC-prone mice, two lines (TgMISIIR-TAg-Low) were isolated that express the oncogenic transgene, but have little or no susceptibility to tumor development. Independent murine ovarian carcinoma (MOVCAR) cell lines were established from the ascites of tumor-bearing C57BL/6 TgMISIIR-TAg transgenic mice, characterized and tested for engraftment in the following recipient mice: 1) severe immunocompromised immunodeficient (SCID), 2) wild type C57BL/6, 3) oophorectomized tumor-prone C57BL/6 TgMISIIR-TAg transgenic and 4) non-tumor prone C57BL/6 TgMISIIR-TAg-Low transgenic. Lastly, MOVCAR cells transduced with a luciferase reporter were implanted in TgMISIIR-TAg-Low mice and in vivo tumor growth monitored by non-invasive optical imaging. Results Engraftment of MOVCAR cells by i.p. injection resulted in the development of disseminated peritoneal carcinomatosis in SCID, but not wild type C57BL/6 mice. Oophorectomized tumor-prone TgMISIIR-TAg mice developed peritoneal carcinomas with high frequency, rendering them unsuitable as allograft recipients. Orthotopic or pseudo-orthotopic implantation of MOVCAR cells in TgMISIIR-TAg-Low mice resulted in the development of disseminated peritoneal tumors, frequently accompanied by the production of malignant ascites. Tumors arising in the engrafted mice bore histopathological resemblance to human high-grade serous EOC and exhibited a similar pattern of peritoneal

  6. Amps particle accelerator definition study

    NASA Technical Reports Server (NTRS)

    Sellen, J. M., Jr.

    1975-01-01

    The Particle Accelerator System of the AMPS (Atmospheric, Magnetospheric, and Plasmas in Space) payload is a series of charged particle accelerators to be flown with the Space Transportation System Shuttle on Spacelab missions. In the configuration presented, the total particle accelerator system consists of an energetic electron beam, an energetic ion accelerator, and both low voltage and high voltage plasma acceleration devices. The Orbiter is illustrated with such a particle accelerator system.

  7. Designing reliability into accelerators

    NASA Astrophysics Data System (ADS)

    Hutton, A.

    1992-07-01

    Future accelerators will have to provide a high degree of reliability. Quality must be designed in right from the beginning and must remain a central theme throughout the project. The problem is similar to the problems facing US industry today, and examples of the successful application of quality engineering will be given. Different aspects of an accelerator project will be addressed: Concept, Design, Motivation, Management Techniques, and Fault Diagnosis. The importance of creating and maintaining a coherent team will be stressed.

  8. Microgravity Acceleration Measurement System

    NASA Technical Reports Server (NTRS)

    Foster, William

    2009-01-01

    Microgravity Acceleration Measurement System (MAMS) is an ongoing study of the small forces (vibrations and accelerations) on the ISS that result from the operation of hardware, crew activities, as well as dockings and maneuvering. Results will be used to generalize the types of vibrations affecting vibration-sensitive experiments. Investigators seek to better understand the vibration environment on the space station to enable future research.

  9. CEBAF Accelerator Achievements

    NASA Astrophysics Data System (ADS)

    Chao, Y. C.; Drury, M.; Hovater, C.; Hutton, A.; Krafft, G. A.; Poelker, M.; Reece, C.; Tiefenback, M.

    2011-05-01

    In the past decade, nuclear physics users of Jefferson Lab's Continuous Electron Beam Accelerator Facility (CEBAF) have benefited from accelerator physics advances and machine improvements. As of early 2011, CEBAF operates routinely at 6 GeV, with a 12 GeV upgrade underway. This article reports highlights of CEBAF's scientific and technological evolution in the areas of cryomodule refurbishment, RF control, polarized source development, beam transport for parity experiments, magnets and hysteresis handling, beam breakup, and helium refrigerator operational optimization.

  10. Breakthrough: Fermilab Accelerator Technology

    ScienceCinema

    None

    2016-07-12

    There are more than 30,000 particle accelerators in operation around the world. At Fermilab, scientists are collaborating with other laboratories and industry to optimize the manufacturing processes for a new type of powerful accelerator that uses superconducting niobium cavities. Experimenting with unique polishing materials, a Fermilab team has now developed an efficient and environmentally friendly way of creating cavities that can propel particles with more than 30 million volts per meter.

  11. Rolamite acceleration sensor

    DOEpatents

    Abbin, Joseph P.; Briner, Clifton F.; Martin, Samuel B.

    1993-01-01

    A rolamite acceleration sensor which has a failsafe feature including a housing, a pair of rollers, a tension band wrapped in an S shaped fashion around the rollers, wherein the band has a force-generation cut out and a failsafe cut out or weak portion. The failsafe cut out or weak portion breaks when the sensor is subjected to an excessive acceleration so that the sensor fails in an open circuit (non-conducting) state permanently.

  12. Rolamite acceleration sensor

    DOEpatents

    Abbin, J.P.; Briner, C.F.; Martin, S.B.

    1993-12-21

    A rolamite acceleration sensor is described which has a failsafe feature including a housing, a pair of rollers, a tension band wrapped in an S shaped fashion around the rollers, wherein the band has a force-generation cut out and a failsafe cut out or weak portion. The failsafe cut out or weak portion breaks when the sensor is subjected to an excessive acceleration so that the sensor fails in an open circuit (non-conducting) state permanently. 6 figures.

  13. Collective field accelerator

    DOEpatents

    Luce, John S.

    1978-01-01

    A collective field accelerator which operates with a vacuum diode and utilizes a grooved cathode and a dielectric anode that operates with a relativistic electron beam with a .nu./.gamma. of .about. 1, and a plurality of dielectric lenses having an axial magnetic field thereabout to focus the collectively accelerated electrons and ions which are ejected from the anode. The anode and lenses operate as unoptimized r-f cavities which modulate and focus the beam.

  14. Oligomerised lychee fruit-derived polyphenol attenuates cognitive impairment in senescence-accelerated mice and endoplasmic reticulum stress in neuronal cells.

    PubMed

    Sakurai, Takuya; Kitadate, Kentaro; Nishioka, Hiroshi; Fujii, Hajime; Ogasawara, Junetsu; Kizaki, Takako; Sato, Shogo; Fujiwara, Tomonori; Akagawa, Kimio; Izawa, Tetsuya; Ohno, Hideki

    2013-11-14

    Recently, the ability of polyphenols to reduce the risk of dementia and Alzheimer's disease (AD) has attracted a great deal of interest. In the present study, we investigated the attenuating effects of oligomerised lychee fruit-derived polyphenol (OLFP, also called Oligonol) on early cognitive impairment. Male senescence-accelerated mouse prone 8 (SAMP8) mice (4 months old) were given OLFP (100 mg/kg per d) for 2 months, and then conditioned fear memory testing was conducted. Contextual fear memory, which is considered hippocampus-dependent memory, was significantly impaired in SAMP8 mice compared with non-senescence-accelerated mice. OLFP attenuated cognitive impairment in SAMP8 mice. Moreover, the results of real-time PCR analysis that followed DNA array analysis in the hippocampus revealed that, compared with SAMP8 mice, the mRNA expression of Wolfram syndrome 1 (Wfs1) was significantly higher in SAMP8 mice administered with OLFP. Wfs1 reportedly helps to protect against endoplasmic reticulum (ER) stress, which is thought to be one of the causes for AD. The expression of Wfs1 was significantly up-regulated in NG108-15 neuronal cells by the treatment with OLFP, and the up-regulation was inhibited by the treatment of the cells with a c-Jun N-terminal kinase-specific inhibitor rather than with an extracellular signal-regulated kinase inhibitor. Moreover, OLFP significantly attenuated the tunicamycin-induced expression of the ER stress marker BiP (immunoglobulin heavy chain-binding protein) in the cells. These results suggest that OLFP has an attenuating effect on early cognitive impairment in SAMP8 mice, and diminishes ER stress in neuronal cells.

  15. Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice.

    PubMed

    Hasegawa-Ishii, Sanae; Inaba, Muneo; Li, Ming; Shi, Ming; Umegaki, Hiroyuki; Ikehara, Susumu; Shimada, Atsuyoshi

    2016-04-01

    Bone marrow-derived cells enter the brain in a non-inflammatory condition through the attachments of choroid plexus and differentiate into ramified myeloid cells. Neurodegenerative conditions may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the dynamics of immune cells migrating from the bone marrow to the brain is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow-bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice as recipients with GFP transgenic B6 mice as donors, and analyzed histologically 4 months later. In the [B6 → 10 mo SAMP10] chimeras, more ramified marrow-derived cells populated a larger number of discrete brain regions than the other chimeras, especially in the diencephalon. Multiplex cytokine assays of the diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G-CSF, CXCL10 and IL-6 than the other groups. Immunohistologically, choroid plexus epithelium and ependyma produced CXCL1, while astrocytic processes in the attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence produced CXCL10, hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to acceleration of the dynamics of marrow-derived cells to the diencephalon. Further studies on the functions of ramified marrow-derived myeloid cells would enhance our understanding of the brain-bone marrow interaction.

  16. Accelerators for America's Future

    NASA Astrophysics Data System (ADS)

    Bai, Mei

    2016-03-01

    Particle accelerator, a powerful tool to energize beams of charged particles to a desired speed and energy, has been the working horse for investigating the fundamental structure of matter and fundermental laws of nature. Most known examples are the 2-mile long Stanford Linear Accelerator at SLAC, the high energy proton and anti-proton collider Tevatron at FermiLab, and Large Hadron Collider that is currently under operation at CERN. During the less than a century development of accelerator science and technology that led to a dazzling list of discoveries, particle accelerators have also found various applications beyond particle and nuclear physics research, and become an indispensible part of the economy. Today, one can find a particle accelerator at almost every corner of our lives, ranging from the x-ray machine at the airport security to radiation diagnostic and therapy in hospitals. This presentation will give a brief introduction of the applications of this powerful tool in fundermental research as well as in industry. Challenges in accelerator science and technology will also be briefly presented

  17. Biomedical accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Freeman, Stewart P. H. T.; Vogel, John S.

    1995-05-01

    Ultrasensitive SIMS with accelerator based spectrometers has recently begun to be applied to biomedical problems. Certain very long-lived radioisotopes of very low natural abundances can be used to trace metabolism at environmental dose levels ( [greater-or-equal, slanted] z mol in mg samples). 14C in particular can be employed to label a myriad of compounds. Competing technologies typically require super environmental doses that can perturb the system under investigation, followed by uncertain extrapolation to the low dose regime. 41Ca and 26Al are also used as elemental tracers. Given the sensitivity of the accelerator method, care must be taken to avoid contamination of the mass spectrometer and the apparatus employed in prior sample handling including chemical separation. This infant field comprises the efforts of a dozen accelerator laboratories. The Center for Accelerator Mass Spectrometry has been particularly active. In addition to collaborating with groups further afield, we are researching the kinematics and binding of genotoxins in-house, and we support innovative uses of our capability in the disciplines of chemistry, pharmacology, nutrition and physiology within the University of California. The field can be expected to grow further given the numerous potential applications and the efforts of several groups and companies to integrate more the accelerator technology into biomedical research programs; the development of miniaturized accelerator systems and ion sources capable of interfacing to conventional HPLC and GMC, etc. apparatus for complementary chemical analysis is anticipated for biomedical laboratories.

  18. Mouse genome database 2016

    PubMed Central

    Bult, Carol J.; Eppig, Janan T.; Blake, Judith A.; Kadin, James A.; Richardson, Joel E.

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data. PMID:26578600

  19. Mouse genome database 2016.

    PubMed

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2016-01-04

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data.

  20. Effects of high salt diets and taurine on the development of hypertension in the stroke-prone spontaneously hypertensive rat.

    PubMed

    Dawson, R; Liu, S; Jung, B; Messina, S; Eppler, B

    2000-01-01

    Taurine is present in high concentrations in mammalian tissues and has been implicated in cardiovascular control mechanisms. The aim of the present study was to evaluate the ability of taurine to attenuate salt-induced elevations in blood pressure and markers of damage to the kidney and cardiovascular system in stroke prone spontaneously hypertensive rats (SPSHR). Male SPSHR (6 weeks old) were placed on high salt diets that contained 1% (w/w) NaCl added to their normal chow for 84 days and then were switched to 3% added NaCl for the remaining 63 days of the study. SPSHR was given 1.5% taurine in the drinking water (n = 8), a taurine free diet (n = 8) or normal chow (n = 8). A final control group (n = 6) was not given high salt diets. High salt diets caused an acceleration in the development of hypertension in all groups. Taurine supplementation reduced ventricular hypertrophy and decreased urinary excretion of protein and creatinine. The taurine free diet did not alter serum or urinary excretion of taurine, but did result in elevated urinary nitrogen excretion, increased serum cholesterol levels, and impaired performance in a spatial learning task. Alterations in dietary taurine intake did not alter urinary or serum electrolytes (Na+, K+), but taurine supplementation did attenuate a rise in serum calcium seen with the high salt diets. Urinary excretion (microg/24h) of epinephrine and dopamine was significantly reduced in SPSHR given 1% NaCl in the diet, but this effect was not seen in SPSHR on taurine free or supplemented diets. Taurine supplementation showed cardioprotective and renoprotective effects in SPSHR given high salt diets.

  1. DEM-based Approaches for the Identification of Flood Prone Areas

    NASA Astrophysics Data System (ADS)

    Samela, Caterina; Manfreda, Salvatore; Nardi, Fernando; Grimaldi, Salvatore; Roth, Giorgio; Sole, Aurelia

    2013-04-01

    The remarkable number of inundations that caused, in the last decades, thousands of deaths and huge economic losses, testifies the extreme vulnerability of many Countries to the flood hazard. As a matter of fact, human activities are often developed in the floodplains, creating conditions of extremely high risk. Terrain morphology plays an important role in understanding, modelling and analyzing the hydraulic behaviour of flood waves. Research during the last 10 years has shown that the delineation of flood prone areas can be carried out using fast methods that relay on basin geomorphologic features. In fact, the availability of new technologies to measure surface elevation (e.g., GPS, SAR, SAR interferometry, RADAR and LASER altimetry) has given a strong impulse to the development of Digital Elevation Models (DEMs) based approaches. The identification of the dominant topographic controls on the flood inundation process is a critical research question that we try to tackle with a comparative analysis of several techniques. We reviewed four different approaches for the morphological characterization of a river basin with the aim to provide a description of their performances and to identify their range of applicability. In particular, we explored the potential of the following tools. 1) The hydrogeomorphic method proposed by Nardi et al. (2006) which defines the flood prone areas according to the water level in the river network through the hydrogeomorphic theory. 2) The linear binary classifier proposed by Degiorgis et al. (2012) which allows distinguishing flood-prone areas using two features related to the location of the site under exam with respect to the nearest hazard source. The two features, proposed in the study, are the length of the path that hydrologically connects the location under exam to the nearest element of the drainage network and the difference in elevation between the cell under exam and the final point of the same path. 3) The method by

  2. LANDSAT imagery analysis: An aid for predicting landslide prone areas for highway construction. [in Arkansas

    NASA Technical Reports Server (NTRS)

    Macdonald, H. C.; Grubbs, R. S.

    1975-01-01

    The most obvious landform features of geologic significance revealed on LANDSAT imagery are linear trends or lineaments. These trends were found to correspond, at least to a large degree, with unmapped faults or complex fracture zones. LANDSAT imagery analysis in northern Arkansas revealed a lineament complex which provides a remarkable correlation with landslide-prone areas along major highway routes. The weathering properties of various rock types, which are considered in designing stable cut slopes and drainage structures, appear to be adversely influenced by the location and trends of LANDSAT defined lineaments. Geologic interpretation of LANDSAT imagery, where applicable and utilized effectively, provides the highway engineer with a tool for predicting and evaluating landslide-prone areas.

  3. Why dissociation and schizotypy overlap: the joint influence of fantasy proneness, cognitive failures, and childhood trauma.

    PubMed

    Giesbrecht, Timo; Merckelbach, Harald; Kater, Maartje; Sluis, Anne Fetsje

    2007-10-01

    A number of studies have noted that dissociative symptoms (e.g., feelings of derealization, depersonalization, memory complaints, absorption) overlap with the tendency to report psychotic-like experiences (i.e., schizotypy). The question arises as to what may account for the shared variance between dissociation and schizotypy. The present study investigated whether fantasy proneness, cognitive failures, and childhood trauma may jointly explain the dissociation-schizotypy link. To this end, we administered the Dissociative Experiences Scale, the Schizotypal Personality Scale, the Creative Experiences Questionnaire, the Cognitive Failures Questionnaire, and the Childhood Trauma Questionnaire to a sample of undergraduates (N = 185). Fantasy proneness, cognitive failures, and childhood trauma together explained substantial part (58%) of the dissociation-schizotypy link. The present study succeeded in explaining a considerate part of the shared variance between dissociation and schizotypy.

  4. Simple shielding reduces dose to the contralateral breast during prone breast cancer radiotherapy

    SciTech Connect

    Goyal, Uma Locke, Angela; Smith-Raymond, Lexie; Georgiev, Georgi N.

    2016-07-01

    Our goal was to design a prone breast shield for the contralateral breast and study its efficacy in decreasing scatter radiation to the contralateral breast in a prone breast phantom setup receiving radiation therapy designed for breast cancer. We constructed a prone breast phantom setup consisting of (1) A thermoplastic mask with a left-sided depression created by a water balloon for a breast shape; (2) 2 plastic bags to hold water in the thermoplastic mask depression; (3) 2000 mL of water to fill the thermoplastic mask depression to create a water-based false breast; (4) 1-cm thick bolus placed in the contralateral breast holder; (5) 2 lead (Pb) sheets, each 0.1-cm thick for blocking scatter radiation in the contralateral bolus-based false breast; (6) a prone breast board to hold the thermoplastic mask, water, bolus, and lead; (7) 9 cm solid water on top of the breast board to simulate body; (8) a diode was used to verify dose for each treatment field of the treated water-based breast; (9) metal–oxide–semiconductor-field effect transistor (MOSFET) dosimeters to measure dose to the contralateral bolus-based breast. The phantom prone breast setup was CT simulated and treatment was designed with 95% isodose line covering the treated breast. The maximum dose was 107.1%. Megavoltage (MV) port images ensured accurate setup. Measurements were done using diodes on the treated water-based breast and MOSFET dosimeters at the medial and lateral sides of the contralateral bolus-based breast without and with the Pb shield. Five treatments were done for each of the 3 data sets and recorded individually for statistical purposes. All treatments were completed with 6 MV photons at 200 cGy per treatment. The dose contributions from each of the 3 data sets including 15 treatments total without and with the prone lead shield to the medial and lateral portions of contralateral bolus-based breast were averaged individually. Unshielded dose means were 37.11 and 2.94 cGy, and

  5. Probability mapping of indoor radon-prone areas using disjunctive kriging.

    PubMed

    Raspa, G; Salvi, F; Torri, G

    2010-01-01

    After a reference to the use of maps of radon-prone areas for indoor radon risk management, and to the methods used to produce them, there is a brief illustration of the geostatistical method of disjunctive kriging (DK) introduced by G. Matheron as a substitute for conditional expectation. There are some good reasons of using this method for the mapping of radon-prone areas as follows: (1) spatial correlation is exploited; (2) unbiasedness is conserved even in the conditions of quasi-stationarity; (3) lognormality of the data is not required; (4) choosing the point estimation allows drawing up smooth probability maps. An application of DK is also presented for the production of probability maps in a campaign of indoor radon measurements conducted by Institute for Environmental Protection and Research, in the provinces of Rome and Viterbo (Central Italy). In the application, it is assessed in particular how much the spatial correlation, even though low, influences the results.

  6. Meralgia Paresthetica after Prone Positioning Ventilation in the Intensive Care Unit

    PubMed Central

    Ballegaard, Martin; Bestle, Morten H.; Tfelt-Hansen, Peer

    2016-01-01

    Meralgia paresthetica (MP) is a mononeuropathy of the lateral femoral cutaneous nerve (LFCN) caused by external compression of the nerve during its course close to the anterior superior iliac spine. We present a case of a patient with acute respiratory distress induced by Legionella pneumonia who was admitted to the intensive care unit (ICU) for mechanical ventilation. In the ICU, the patient received one session of prone position ventilation for 8.5 consecutive hours. At evaluation six months later, the patient reported persistent bilateral numbness of the anterolateral thigh, which he complained had begun right after he woke up at the ICU. He was referred for further neurological and neurophysiological examination and was diagnosed with bilateral MP, a condition never previously described as a complication to mechanical ventilation in prone position in the ICU. PMID:27752369

  7. The Prone Position During Surgery and its Complications: A Systematic Review and Evidence-Based Guidelines

    PubMed Central

    Kwee, Melissa M.; Ho, Yik-Hong; Rozen, Warren M.

    2015-01-01

    Surgery in the prone position is often a necessity when access to posterior anatomic structures is required. However, many complications are known to be associated with this type of surgery, as physiologic changes occur with increased pressure to anterior structures. While several studies have discussed postoperative vision loss, much fewer studies with lower levels of evidence have addressed other complications. A systematic literature review was conducted using 2 different databases, and 53 papers were regarded as appropriate for inclusion. Qualitative and quantitative analysis was performed. Thirteen complications were identified. Postoperative vision loss and cardiovascular complications, including hypovolemia and cardiac arrest, had the most number of studies and highest level of evidence. Careful planning for optimal positioning, padding, timing, as well as increased vigilance are evidence-based recommendations where operative prone positioning is required. PMID:25692433

  8. Simple shielding reduces dose to the contralateral breast during prone breast cancer radiotherapy.

    PubMed

    Goyal, Uma; Locke, Angela; Smith-Raymond, Lexie; Georgiev, Georgi N

    2016-01-01

    Our goal was to design a prone breast shield for the contralateral breast and study its efficacy in decreasing scatter radiation to the contralateral breast in a prone breast phantom setup receiving radiation therapy designed for breast cancer. We constructed a prone breast phantom setup consisting of (1) A thermoplastic mask with a left-sided depression created by a water balloon for a breast shape; (2) 2 plastic bags to hold water in the thermoplastic mask depression; (3) 2000mL of water to fill the thermoplastic mask depression to create a water-based false breast; (4) 1-cm thick bolus placed in the contralateral breast holder; (5) 2 lead (Pb) sheets, each 0.1-cm thick for blocking scatter radiation in the contralateral bolus-based false breast; (6) a prone breast board to hold the thermoplastic mask, water, bolus, and lead; (7) 9cm solid water on top of the breast board to simulate body; (8) a diode was used to verify dose for each treatment field of the treated water-based breast; (9) metal-oxide-semiconductor-field effect transistor (MOSFET) dosimeters to measure dose to the contralateral bolus-based breast. The phantom prone breast setup was CT simulated and treatment was designed with 95% isodose line covering the treated breast. The maximum dose was 107.1%. Megavoltage (MV) port images ensured accurate setup. Measurements were done using diodes on the treated water-based breast and MOSFET dosimeters at the medial and lateral sides of the contralateral bolus-based breast without and with the Pb shield. Five treatments were done for each of the 3 data sets and recorded individually for statistical purposes. All treatments were completed with 6MV photons at 200cGy per treatment. The dose contributions from each of the 3 data sets including 15 treatments total without and with the prone lead shield to the medial and lateral portions of contralateral bolus-based breast were averaged individually. Unshielded dose means were 37.11 and 2.94cGy, and shielded dose

  9. Thoracic disc herniation: An unusual complication after prone positioning in spinal surgery

    PubMed Central

    Ebrahim, Mohammed Zahier; Vlok, Adriaan J.

    2016-01-01

    Neurological complications of the prone position have been well documented. Post-operative paraplegia and neurological deterioration unrelated to the site of surgery after proning in spinal surgery is a rare but potentially devastating complication. We describe the case of a 47 year old female who underwent an L4/5 discectomy and posterior instrumented fusion. A few hours after surgery she developed bilateral lower limb weakness with a T11 sensory level. Post-operative MRI revealed an acute disc herniation at the T11/12 level with associated spinal cord compression. This was not present on the pre-operative imaging. A subsequent T11/12 discectomy and instrumented fusion was performed and the patient's motor and sensory function returned to normal.

  10. Left-sided thoracoscopy in the prone position for surgery of distal esophageal benign pathologies

    PubMed Central

    Issaka, Adamu; Kara, Hasan Volkan; Eldem, Barkin

    2014-01-01

    Exposure of the distal esophagus can be achieved by a wide variety of surgical approaches. The standard procedure is mostly by laparoscopy. In cases where laparoscopy is relatively contraindicated, thoracoscopy is preferred. In this case, exposure of the distal esophagus from the aorta, heart and lung is technically challenging using thoracoscopy in the right lateral decubitus position. Surgery in the prone position for esophageal cancer has been successfully described in previous literature. We present our experience with left-sided thoracoscopy in the prone position in three patients with benign distal esophageal pathologies. This approach provided a much better exposure of the distal esophagus and enabled a successful surgery to be done in all patients with less manipulation of the lung. PMID:27489640

  11. The effect of auditory verbal imagery on signal detection in hallucination-prone individuals

    PubMed Central

    Moseley, Peter; Smailes, David; Ellison, Amanda; Fernyhough, Charles

    2016-01-01

    Cognitive models have suggested that auditory hallucinations occur when internal mental events, such as inner speech or auditory verbal imagery (AVI), are misattributed to an external source. This has been supported by numerous studies indicating that individuals who experience hallucinations tend to perform in a biased manner on tasks that require them to distinguish self-generated from non-self-generated perceptions. However, these tasks have typically been of limited relevance to inner speech models of hallucinations, because they have not manipulated the AVI that participants used during the task. Here, a new paradigm was employed to investigate the interaction between imagery and perception, in which a healthy, non-clinical sample of participants were instructed to use AVI whilst completing an auditory signal detection task. It was hypothesized that AVI-usage would cause participants to perform in a biased manner, therefore falsely detecting more voices in bursts of noise. In Experiment 1, when cued to generate AVI, highly hallucination-prone participants showed a lower response bias than when performing a standard signal detection task, being more willing to report the presence of a voice in the noise. Participants not prone to hallucinations performed no differently between the two conditions. In Experiment 2, participants were not specifically instructed to use AVI, but retrospectively reported how often they engaged in AVI during the task. Highly hallucination-prone participants who retrospectively reported using imagery showed a lower response bias than did participants with lower proneness who also reported using AVI. Results are discussed in relation to prominent inner speech models of hallucinations. PMID:26435050

  12. Long-term Clinical Outcomes of Whole-Breast Irradiation Delivered in the Prone Position

    SciTech Connect

    Stegman, Lauren D.; Beal, Katherine P.; Hunt, Margie A.; Fornier, Monica N.; McCormick, Beryl . E-mail: mccormib@mskcc.org

    2007-05-01

    Purpose: The aim of this study was to evaluate retrospectively the effectiveness and toxicity of post-lumpectomy whole-breast radiation therapy delivered with prone positioning. Methods and Materials: Between September 1992 and August 2004, 245 women with 248 early-stage invasive or in situ breast cancers were treated using a prone breast board. Photon fields treated the whole breast to 46 to 50.4 Gy with standard fractionation. The target volume was clinically palpable breast tissue; no attempt was made to irradiate chest wall lymphatics. Tumor bed boosts were delivered in 85% of cases. Adjuvant chemotherapy and hormonal therapy were administered to 42% and 62% of patients, respectively. Results: After a median follow-up of 4.9 years, the 5 year actuarial true local and elsewhere ipsilateral breast tumor recurrence rates were 4.8% and 1.3%, respectively. The 5-year actuarial rates of regional nodal recurrence and distant metastases were 1.6% and 7.4%. Actuarial disease-free, disease-specific, and overall survival rates at 5 years were 89.4%, 97.3%, and 93%, respectively. Treatment breaks were required by 2.4% of patients. Grade 3 acute dermatitis and edema were each limited to 2% of patients. Only 4.9% of patients complained of acute chest wall discomfort. Chronic Grade 2 to 3 skin and subcutaneous tissue toxicities were reported in 4.4% and 13.7% of patients, respectively. Conclusions: Prone position breast radiation results in similar long-term disease control with a favorable toxicity profile compared with standard supine tangents. The anatomic advantages of prone positioning may contribute to improving the therapeutic ratio of post-lumpectomy radiation by improving dose homogeneity and minimizing incidental cardiac and lung dose.

  13. Electromagnetic Tracking of Intrafraction Prostate Displacement in Patients Externally Immobilized in the Prone Position

    SciTech Connect

    Bittner, Nathan; Wallner, Kent E.; Merrick, Gregory S.

    2010-06-01

    Purpose: To evaluate intrafraction prostate displacement among patients immobilized in the prone position using real-time monitoring of implanted radiofrequency transponders. Methods and Materials: The Calypso localization system was used to track prostate motion in patients receiving external beam radiation therapy (XRT) for prostate cancer. All patients were treated in the prone position and immobilized with a thermoplastic immobilization device. Real-time measurement of prostate displacement was recorded for each treatment fraction. These measurements were used to determine the duration and magnitude of displacement along the three directional axes. Results: The calculated centroid of the implanted transponders was offset from the treatment isocenter by >=2 mm, >=3 mm, and >=4 mm for 38.0%, 13.9%, and 4.5% of the time. In the lateral dimension, the centroid was offset from the treatment isocenter by >=2 mm, >=3 mm, and >=4 mm for 2.7%, 0.4%, and 0.06% of the time. In the superior-inferior dimension, the centroid was offset from the treatment isocenter by >=2 mm, >=3 mm, and >=4 mm for 16.1%, 4.7%, and 1.5% of the time, respectively. In the anterior-posterior dimension, the centroid was offset from the treatment isocenter by >=2 mm, >=3 mm, and >=4 mm for 13.4%, 3.0%, and 0.5% of the time. Conclusions: Intrafraction prostate displacement in the prone position is comparable to that in the supine position. For patients with large girth, in whom the supine position may preclude accurate detection of implanted radiofrequency transponders, treatment in the prone position is a suitable alternative.

  14. Random Mutagenesis by Error-Prone Polymerase Chain Reaction Using a Heavy Water Solvent.

    PubMed

    Minamoto, Toshifumi

    2017-01-01

    Heavy water is a form of water that contains a heavier isotope of hydrogen ((2)H, also known as deuterium, D) or oxygen ((17)O or (18)O). When using heavy water as a solvent, error-prone polymerase chain reaction (epPCR) can induce random mutations independent of the polymerase used or the composition of the PCR reaction mixture. This relatively new method can easily be combined with the existing epPCR methods to increase the rate of mutations.

  15. Anesthetic Management of the Parturient for Lumbar Disc Surgery in the Prone Position

    PubMed Central

    Martel, Colleen G.; Volpi-Abadie, Jacqueline; Ural, Kelly

    2015-01-01

    Background While back pain is common in pregnancy, urgent surgical intervention is rarely required. Case Report A parturient in the third trimester presented with foot drop and sensory deficits. Surgical intervention was deemed necessary and was performed in the prone position to facilitate exposure. A multidisciplinary approach was vital to the management plan. Conclusion For any pregnant patient undergoing nonobstetric surgery, the care provided should be individualized and thoughtful, keeping in mind both the mother and fetus. PMID:26412999

  16. Registration of prone and supine CT colonography scans using correlation optimized warping and canonical correlation analysis

    SciTech Connect

    Wang Shijun; Yao Jianhua; Liu Jiamin; Petrick, Nicholas; Van Uitert, Robert L.; Periaswamy, Senthil; Summers, Ronald M.

    2009-12-15

    Purpose: In computed tomographic colonography (CTC), a patient will be scanned twice--Once supine and once prone--to improve the sensitivity for polyp detection. To assist radiologists in CTC reading, in this paper we propose an automated method for colon registration from supine and prone CTC scans. Methods: We propose a new colon centerline registration method for prone and supine CTC scans using correlation optimized warping (COW) and canonical correlation analysis (CCA) based on the anatomical structure of the colon. Four anatomical salient points on the colon are first automatically distinguished. Then correlation optimized warping is applied to the segments defined by the anatomical landmarks to improve the global registration based on local correlation of segments. The COW method was modified by embedding canonical correlation analysis to allow multiple features along the colon centerline to be used in our implementation. Results: We tested the COW algorithm on a CTC data set of 39 patients with 39 polyps (19 training and 20 test cases) to verify the effectiveness of the proposed COW registration method. Experimental results on the test set show that the COW method significantly reduces the average estimation error in a polyp location between supine and prone scans by 67.6%, from 46.27{+-}52.97 to 14.98 mm{+-}11.41 mm, compared to the normalized distance along the colon centerline algorithm (p<0.01). Conclusions: The proposed COW algorithm is more accurate for the colon centerline registration compared to the normalized distance along the colon centerline method and the dynamic time warping method. Comparison results showed that the feature combination of z-coordinate and curvature achieved lowest registration error compared to the other feature combinations used by COW. The proposed method is tolerant to centerline errors because anatomical landmarks help prevent the propagation of errors across the entire colon centerline.

  17. Clinical review: Intra-abdominal hypertension: does it influence the physiology of prone ventilation?

    PubMed

    Kirkpatrick, Andrew W; Pelosi, Paolo; De Waele, Jan J; Malbrain, Manu Lng; Ball, Chad G; Meade, Maureen O; Stelfox, Henry T; Laupland, Kevin B

    2010-01-01

    Prone ventilation (PV) is a ventilatory strategy that frequently improves oxygenation and lung mechanics in critical illness, yet does not consistently improve survival. While the exact physiologic mechanisms related to these benefits remain unproven, one major theoretical mechanism relates to reducing the abdominal encroachment upon the lungs. Concurrent to this experience is increasing recognition of the ubiquitous role of intra-abdominal hypertension (IAH) in critical illness, of the relationship between IAH and intra-abdominal volume or thus the compliance of the abdominal wall, and of the potential difference in the abdominal influences between the extrapulmonary and pulmonary forms of acute respiratory distress syndrome. The present paper reviews reported data concerning intra-abdominal pressure (IAP) in association with the use of PV to explore the potential influence of IAH. While early authors stressed the importance of gravitationally unloading the abdominal cavity to unencumber the lung bases, this admonition has not been consistently acknowledged when PV has been utilized. Basic data required to understand the role of IAP/IAH in the physiology of PV have generally not been collected and/or reported. No randomized controlled trials or meta-analyses considered IAH in design or outcome. While the act of proning itself has a variable reported effect on IAP, abundant clinical and laboratory data confirm that the thoracoabdominal cavities are intimately linked and that IAH is consistently transmitted across the diaphragm--although the transmission ratio is variable and is possibly related to the compliance of the abdominal wall. Any proning-related intervention that secondarily influences IAP/IAH is likely to greatly influence respiratory mechanics and outcomes. Further study of the role of IAP/IAH in the physiology and outcomes of PV in hypoxemic respiratory failure is thus required. Theories relating inter-relations between prone positioning and the

  18. Severe acute respiratory distress syndrome in a child with malaria: favorable response to prone positioning.

    PubMed

    Flores, Jose C; Imaz, Ana; López-Herce, Jesús; Seriñá, Carlota

    2004-03-01

    We present the case of a 4-year-old boy with malaria who developed acute respiratory distress syndrome with severe hypoxemia refractory to mechanical ventilation and inhaled nitric oxide. Placing the patient in prone position immediately and persistently improved oxygenation: the ratio of P(aO(2)) to fraction of inspired oxygen rose from 47 to 180 mm Hg and the oxygenation index decreased from 40 to 11. The patient survived, with no respiratory sequelae.

  19. Rosuvastatin Treatment Prevents Progressive Kidney Inflammation and Fibrosis in Stroke-Prone Rats

    PubMed Central

    Gianella, Anita; Nobili, Elena; Abbate, Mauro; Zoja, Carla; Gelosa, Paolo; Mussoni, Luciana; Bellosta, Stefano; Canavesi, Monica; Rottoli, Daniela; Guerrini, Uliano; Brioschi, Maura; Banfi, Cristina; Tremoli, Elena; Remuzzi, Giuseppe; Sironi, Luigi

    2007-01-01

    Salt-loaded, spontaneously hypertensive stroke-prone rats show progressive increases in blood pressure and proteinuria and accumulate acute-phase proteins in body fluids, modeling events during renal damage. The aim of this study was to assess the pathological events occurring in the kidney of spontaneously hypertensive stroke-prone rats over time and evaluate the effects of statin treatment, which is known to improve renal and cardiovascular outcomes. Kidneys of male spontaneously hypertensive stroke-prone rats euthanized at different stages of proteinuria showed progressive inflammatory cell infiltration, the accumulation of α-smooth muscle actin-positive cells, degenerative changes in podocytes, and severe fibrosis. These were accompanied by an imbalance in the plasminogen/plasmin and metalloprotease systems characterized by the increased renal expression of plasminogen activator inhibitor-1, tissue plasminogen activator, and urokinase plasminogen activator; the net result was an increase in plasmin and matrix metalloproteinase (MMP)-2 and a reduction in MMP-9 activity. Chronic treatment with the hydrophilic rosuvastatin had renoprotective effects in terms of morphology and inflammation and prevented the changes in plasmin, MMP-2, and MMP-9 activity. These effects were independent of the changes in blood pressure and plasma lipid levels. Treatment with the lipophilic simvastatin was not renoprotective. These data suggest that rosuvastatin may have potential utility as a therapeutic option in renal diseases that are characterized by inflammation and fibrosis. PMID:17392157

  20. Psychological performance of accident-prone automobile drivers in China: a case-control study.

    PubMed

    Jin, H Q; Araki, S; Wu, X K; Zhang, Y W; Yokoyama, K

    1991-03-01

    To evaluate the role of neurobehavioural factors in the aetiology of recurrent automobile accidents, we administered the Revised Wechsler Adult Intelligence Scale (WAIS-R), the Eysenck Personality Questionnaire (EPQ), and choice and simple reaction time tests to 31 accident-prone automobile drivers. These drivers who had caused three or more traffic accidents during the years 1980-1984, were selected from records of 2723 traffic accidents registered by Hefei Traffic Police Department during the years 1980-1984. The same tests were administered to an equal number of sex- and age-matched control drivers who had no reported involvement in automobile accidents. None of the subjects had suffered from any neuropsychiatric illness or head injury. Comparisons between the two groups indicated that for accident-prone drivers scores on picture completion and block design subtests of the WAIS-R were significantly lowered (p less than 0.05); scores for neurosis extrovert behaviour and psychosis (EPQ) were significantly higher (p less than 0.05); and the number of errors in the choice reaction time test was significantly higher (p less than 0.01). It is suggested that accident-prone drivers have lower psychological performance, poorer judgement and a higher tendency than safe drivers to be neurotic, extrovert and psychotic.

  1. Factors associated with larval control practices in a dengue outbreak prone area.

    PubMed

    Mohamad, Mariam; Selamat, Mohamad Ikhsan; Ismail, Zaliha

    2014-01-01

    In order to reduce the risk of dengue outbreak recurrence in a dengue outbreak prone area, the members of the community need to sustain certain behavior to prevent mosquito from breeding. Our study aims to identify the factors associated with larval control practices in this particular community. A cross-sectional study involves 322 respondents living in a dengue outbreak prone area who were interviewed using a pretested questionnaire. The level of knowledge about Aedes mosquitoes, dengue transmission, its symptoms, and personal preventive measures ranges from fair to good. The level of attitude towards preventive measures was high. However, reported level of personal larval control practices was low (33.2%). Our multiple logistic regression analysis showed that only those with a good level of attitude towards personal preventive measure and frequent attendance to health campaigns were significantly associated with the good larval control practices. We conclude that, in a dengue outbreak prone area, having a good attitude towards preventive measures and frequent participation in health campaigns are important factors to sustain practices on larval control.

  2. Random mutagenesis by error-prone pol plasmid replication in Escherichia coli.

    PubMed

    Alexander, David L; Lilly, Joshua; Hernandez, Jaime; Romsdahl, Jillian; Troll, Christopher J; Camps, Manel

    2014-01-01

    Directed evolution is an approach that mimics natural evolution in the laboratory with the goal of modifying existing enzymatic activities or of generating new ones. The identification of mutants with desired properties involves the generation of genetic diversity coupled with a functional selection or screen. Genetic diversity can be generated using PCR or using in vivo methods such as chemical mutagenesis or error-prone replication of the desired sequence in a mutator strain. In vivo mutagenesis methods facilitate iterative selection because they do not require cloning, but generally produce a low mutation density with mutations not restricted to specific genes or areas within a gene. For this reason, this approach is typically used to generate new biochemical properties when large numbers of mutants can be screened or selected. Here we describe protocols for an advanced in vivo mutagenesis method that is based on error-prone replication of a ColE1 plasmid bearing the gene of interest. Compared to other in vivo mutagenesis methods, this plasmid-targeted approach allows increased mutation loads and facilitates iterative selection approaches. We also describe the mutation spectrum for this mutagenesis methodology in detail, and, using cycle 3 GFP as a target for mutagenesis, we illustrate the phenotypic diversity that can be generated using our method. In sum, error-prone Pol I replication is a mutagenesis method that is ideally suited for the evolution of new biochemical activities when a functional selection is available.

  3. Non-invasive ventilation in prone position for refractory hypoxemia after bilateral lung transplantation.

    PubMed

    Feltracco, Paolo; Serra, Eugenio; Barbieri, Stefania; Persona, Paolo; Rea, Federico; Loy, Monica; Ori, Carlo

    2009-01-01

    Temporary graft dysfunction with gas exchange abnormalities is a common finding during the postoperative course of a lung transplant and is often determined by the post-reimplantation syndrome. Supportive measures including oxygen by mask, inotropes, diuretics, and pulmonary vasodilators are usually effective in non-severe post-reimplantation syndromes. However, in less-responsive clinical pictures, tracheal intubation with positive pressure ventilation, or non-invasive positive pressure ventilation (NIV), is necessary. We report on the clinical course of two patients suffering from refractory hypoxemia due to post-reimplantation syndrome treated with NIV in the prone and Trendelenburg positions. NIV was well tolerated and led to resolution of atelectactic areas and dishomogeneous lung infiltrates. Repeated turning from supine to prone under non invasive ventilation determined a stable improvement of gas exchange and prevented a more invasive approach. Even though NIV in the prone position has not yet entered into clinical practice, it could be an interesting option to achieve a better match between ventilation and perfusion. This technique, which we successfully applied in lung transplantation, can be easily extended to other lung diseases with non-recruitable dorso-basal areas.

  4. The Chapman psychosis-proneness scales: Consistency across culture and time.

    PubMed

    Chan, Raymond C K; Shi, Hai-song; Geng, Fu-lei; Liu, Wen-hua; Yan, Chao; Wang, Yi; Gooding, Diane C

    2015-07-30

    The purpose of the present study was to examine the factor structure and the temporal stability of the Chapman psychosis-proneness scales in a representative sample of nonclinical Chinese young adults. The four psychosis-proneness scales evaluated were the Perceptual Aberration (PAS), Magical Ideation (MIS), revised Social Anhedonia (RSAS), and revised Physical Anhedonia (RPAS) scales. The sample consisted of 1724 young adults with a mean age of 18.8 years (S.D. = 0.84). The results of the confirmatory factor analyses indicated that the best fitting model was a two-factor model with positive schizotypy (PER and MIS) scales and negative schizotypy (RSAS and RPAS) scales. The data add to the growing literature indicating that the measurement of schizotypal traits is consistent across cultures. In addition, the results support the measurement invariance of the Chapman psychosis-proneness scales across time, i.e., there was ample evidence of test-retest reliability over a test interval of 6 months.

  5. Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation.

    PubMed

    Stavnezer, Janet; Linehan, Erin K; Thompson, Mikayla R; Habboub, Ghaith; Ucher, Anna J; Kadungure, Tatenda; Tsuchimoto, Daisuke; Nakabeppu, Yusaku; Schrader, Carol E

    2014-06-24

    Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase β. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B cells, is expressed at very low levels in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency has very little effect on SHM. In contrast, the less efficient homolog, APE2, is highly expressed and contributes not only to the frequency of mutations, but also to the generation of mutations at A:T base pair (bp), insertions, and deletions. In the absence of both UNG and APE2, mutations at A:T bp are dramatically reduced. Single-strand breaks generated by APE2 could provide entry points for exonuclease recruited by the mismatch repair proteins Msh2-Msh6, and the known association of APE2 with proliferating cell nuclear antigen could recruit translesion polymerases to create mutations at AID-induced lesions and also at A:T bp. Our data provide new insight into error-prone repair of AID-induced lesions, which we propose is facilitated by down-regulation of APE1 and up-regulation of APE2 expression in germinal center B cells.

  6. Alternated Prone and Supine Whole-Breast Irradiation Using IMRT: Setup Precision, Respiratory Movement and Treatment Time

    SciTech Connect

    Veldeman, Liv; De Gersem, Werner; Speleers, Bruno; Truyens, Bart; Van Greveling, Annick; Van den Broecke, Rudy; De Neve, Wilfried

    2012-04-01

    Purpose: The objective of this study was to compare setup precision, respiration-related breast movement and treatment time between prone and supine positions for whole-breast irradiation. Methods and Materials: Ten patients with early-stage breast carcinoma after breast-conserving surgery were treated with prone and supine whole breast-irradiation in a daily alternating schedule. Setup precision was monitored using cone-beam computed tomography (CBCT) imaging. Respiration-related breast movement in the vertical direction was assessed by magnetic sensors. The time needed for patient setup and for the CBCT procedure, the beam time, and the length of the whole treatment slot were also recorded. Results: Random and systematic errors were not significantly different between positions in individual patients for each of the three axes (left-right, longitudinal, and vertical). Respiration-related movement was smaller in prone position, but about 80% of observations showed amplitudes <1 mm in both positions. Treatment slots were longer in prone position (21.2 {+-} 2.5 min) than in supine position (19.4 {+-} 0.8 min; p = 0.044). Conclusion: Comparison of setup precision between prone and supine position in the same patient showed no significant differences in random and systematic errors. Respiratory movement was smaller in prone position. The longer treatment slots in prone position can probably be attributed to the higher repositioning need.

  7. The Benefits of Prone SPECT Myocardial Perfusion Imaging in Reducing Both Artifact Defects and Patient Radiation Exposure

    PubMed Central

    Stathaki, Maria; Koukouraki, Sophia; Papadaki, Emmanouela; Tsaroucha, Angeliki; Karkavitsas, Nikolaos

    2015-01-01

    Background Prone imaging has been demonstrated to minimize diaphragmatic and breast tissue attenuation. Objectives To determine the role of prone imaging on the reduction of unnecessary rest perfusion studies and coronary angiographies performed, thus decreasing investigation time and radiation exposure. Methods We examined 139 patients, 120 with an inferior wall and 19 with an anterior wall perfusion defect that might represented attenuation artifact. Post-stress images were acquired in both the supine and prone position. Coronary angiography was used as the “gold standard” for evaluating coronary artery patency. The study was terminated and rest imaging was obviated in the presence of complete improvement of the defect in the prone position. Quantitative interpretation was performed. Results were compared with clinical data and coronary angiographic findings. Results Prone acquisition correctly revealed defect improvement in 89 patients (89/120) with inferior wall and 12 patients (12/19) with anterior wall attenuation artifact. Quantitative analysis demonstrated statistically significant difference in the mean summed stress scores (SSS) of supine and mean SSS of prone studies in patients with disappearing inferior wall defect in the prone position and patent right coronary artery (true negative results). The mean difference between SSS in supine and in prone position was higher with disappearing than with remaining defects. Conclusion Technetium-99m (Tc-99m) tetrofosmin myocardial perfusion imaging with the patient in the prone position overcomes soft tissue attenuation; moreover it provides an inexpensive, accurate approach to limit the number of unnecessary rest perfusion studies and coronary angiographies performed. PMID:26559981

  8. Mitochondrial Dysfunction in the Liver and Antiphospholipid Antibody Production Precede Disease Onset and Respond to Rapamycin in Lupus‐Prone Mice

    PubMed Central

    Oaks, Zachary; Winans, Thomas; Caza, Tiffany; Fernandez, David; Liu, Yuxin; Landas, Steve K.; Banki, Katalin

    2016-01-01

    Objective Antiphospholipid antibodies (aPL) constitute a diagnostic criterion of systemic lupus erythematosus (SLE), and aPL have been functionally linked to liver disease in patients with SLE. Since the mechanistic target of rapamycin (mTOR) is a regulator of oxidative stress, a pathophysiologic process that contributes to the development of aPL, this study was undertaken in a mouse model of SLE to examine the involvement of liver mitochondria in lupus pathogenesis. Methods Mitochondria were isolated from lupus‐prone MRL/lpr, C57BL/6.lpr, and MRL mice, age‐matched autoimmunity‐resistant C57BL/6 mice as negative controls, and transaldolase‐deficient mice, a strain that exhibits oxidative stress in the liver. Electron transport chain (ETC) activity was assessed using measurements of oxygen consumption. ETC proteins, which are regulators of mitochondrial homeostasis, and the mTOR complexes mTORC1 and mTORC2 were examined by Western blotting. Anticardiolipin (aCL) and anti–β2‐glycoprotein I (anti‐β2GPI) autoantibodies were measured by enzyme‐linked immunosorbent assay in mice treated with rapamycin or mice treated with a solvent control. Results Mitochondrial oxygen consumption was increased in the livers of 4‐week‐old, disease‐free MRL/lpr mice relative to age‐matched controls. Levels of the mitophagy initiator dynamin‐related protein 1 (Drp1) were depleted while the activity of mTORC1 was increased in MRL/lpr mice. In turn, mTORC2 activity was decreased in MRL and MRL/lpr mice. In addition, levels of aCL and anti‐β2GPI were elevated preceding the development of nephritis in 4‐week‐old MRL, C57BL/6.lpr, and MRL/lpr mice. Transaldolase‐deficient mice showed increased oxygen consumption, depletion of Drp1, activation of mTORC1, and elevated expression of NADH:ubiquinone oxidoreductase core subunit S3 (NDUFS3), a pro‐oxidant subunit of ETC complex I, as well as increased production of aCL and anti‐β2GPI autoantibodies. Treatment

  9. Laser Ion Acceleration Control

    NASA Astrophysics Data System (ADS)

    Kawata, Shigeo; Nagashima, T.; Izumiyama, T.; Sato, D.; Takano, M.; Barada, D.; Ma, Y. Y.; Gu, Y. J.; Kong, Q.; Wang, P. X.; Wang, W. M.

    2013-10-01

    An intense femtosecond pulsed laser is employed to accelerate ions. The issues in the laser ion accelerator include the energy efficiency from the laser to the ions, the ion beam collimation, the ion energy spectrum control, the ion beam bunching, the ion particle energy control, etc. In the study particle computer simulations were performed to solve the issues, and each component was designed to control the ion beam quality. When an intense laser illuminates a target, electrons in the target are accelerated and leave from the target; temporarily a strong electric field is formed between the high-energy electrons and the target ions, and the target ions are accelerated. The energy efficiency from the laser to ions was improved by using a solid target with a fine sub-wavelength structure or by a near critical density gas plasma. The ion beam collimation was realized by holes behind the solid target. The control of the ion energy spectrum and the ion particle energy, and the ion beam bunching were successfully realized by a multi-stage laser-target interaction. The present study proposed a novel concept for a future compact laser ion accelerator, based on each component study required to control the ion beam quality and parameters. Partly supported by JSPS, MEXT, CORE, Japan/US Cooperation program, ASHULA and ILE/Osaka University.

  10. Dielectric laser accelerators

    NASA Astrophysics Data System (ADS)

    England, R. Joel; Noble, Robert J.; Bane, Karl; Dowell, David H.; Ng, Cho-Kuen; Spencer, James E.; Tantawi, Sami; Wu, Ziran; Byer, Robert L.; Peralta, Edgar; Soong, Ken; Chang, Chia-Ming; Montazeri, Behnam; Wolf, Stephen J.; Cowan, Benjamin; Dawson, Jay; Gai, Wei; Hommelhoff, Peter; Huang, Yen-Chieh; Jing, Chunguang; McGuinness, Christopher; Palmer, Robert B.; Naranjo, Brian; Rosenzweig, James; Travish, Gil; Mizrahi, Amit; Schachter, Levi; Sears, Christopher; Werner, Gregory R.; Yoder, Rodney B.

    2014-10-01

    The use of infrared lasers to power optical-scale lithographically fabricated particle accelerators is a developing area of research that has garnered increasing interest in recent years. The physics and technology of this approach is reviewed, which is referred to as dielectric laser acceleration (DLA). In the DLA scheme operating at typical laser pulse lengths of 0.1 to 1 ps, the laser damage fluences for robust dielectric materials correspond to peak surface electric fields in the GV /m regime. The corresponding accelerating field enhancement represents a potential reduction in active length of the accelerator between 1 and 2 orders of magnitude. Power sources for DLA-based accelerators (lasers) are less costly than microwave sources (klystrons) for equivalent average power levels due to wider availability and private sector investment. Because of the high laser-to-particle coupling efficiency, required pulse energies are consistent with tabletop microJoule class lasers. Combined with the very high (MHz) repetition rates these lasers can provide, the DLA approach appears promising for a variety of applications, including future high-energy physics colliders, compact light sources, and portable medical scanners and radiative therapy machines.

  11. Electrostatic Plasma Accelerator (EPA)

    NASA Technical Reports Server (NTRS)

    Brophy, John R.; Aston, Graeme

    1989-01-01

    The Electrostatic Plasma Accelerator (EPA) is a thruster concept which promises specific impulse levels between low power arcjets and those of the ion engine while retaining the relative simplicity of the arcjet. The EPA thruster produces thrust through the electrostatic acceleration of a moderately dense plasma. No accelerating electrodes are used and the specific impulse is a direct function of the applied discharge voltage and the propellant atomic mass. The goal of the present program is to demonstrate feasibility of the EPA thruster concept through experimental and theoretical investigations of the EPA acceleration mechanism and discharge chamber performance. Experimental investigations will include operating the test bed ion (TBI) engine as an EPA thruster and parametrically varying the thruster geometry and operating conditions to quantify the electrostatic plasma acceleration effect. The theoretical investigations will include the development of a discharge chamber model which describes the relationships between the engine size, plasma properties, and overall performance. For the EPA thruster to be a viable propulsion concept, overall thruster efficiencies approaching 30% with specific impulses approaching 1000 s must be achieved.

  12. Advanced accelerator theory development

    SciTech Connect

    Sampayan, S.E.; Houck, T.L.; Poole, B.; Tishchenko, N.; Vitello, P.A.; Wang, I.

    1998-02-09

    A new accelerator technology, the dielectric wall accelerator (DWA), is potentially an ultra compact accelerator/pulsed power driver. This new accelerator relies on three new components: the ultra-high gradient insulator, the asymmetric Blumlein and low jitter switches. In this report, we focused our attention on the first two components of the DWA system the insulators and the asymmetric Blumlein. First, we sought to develop the necessary design tools to model and scale the behavior of the high gradient insulator. To perform this task we concentrated on modeling the discharge processes (i.e., initiation and creation of the surface discharge). In addition, because these high gradient structures exhibit favorable microwave properties in certain accelerator configurations, we performed experiments and calculations to determine the relevant electromagnetic properties. Second, we performed circuit modeling to understand energy coupling to dynamic loads by the asymmetric Blumlein. Further, we have experimentally observed a non-linear coupling effect in certain asymmetric Blumlein configurations. That is, as these structures are stacked into a complete module, the output voltage does not sum linearly and a lower than expected output voltage results. Although we solved this effect experimentally, we performed calculations to understand this effect more fully to allow better optimization of this DWA pulse-forming line system.

  13. Plasma-based accelerator structures

    SciTech Connect

    Schroeder, Carl B.

    1999-12-01

    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas.

  14. Perturbations for transient acceleration

    SciTech Connect

    Vargas, Cristofher Zuñiga; Zimdahl, Winfried; Hipólito-Ricaldi, Wiliam S. E-mail: hipolito@ceunes.ufes.br

    2012-04-01

    According to the standard ΛCDM model, the accelerated expansion of the Universe will go on forever. Motivated by recent observational results, we explore the possibility of a finite phase of acceleration which asymptotically approaches another period of decelerated expansion. Extending an earlier study on a corresponding homogeneous and isotropic dynamics, in which interactions between dark matter and dark energy are crucial, the present paper also investigates the dynamics of the matter perturbations both on the Newtonian and General Relativistic (GR) levels and quantifies the potential relevance of perturbations of the dark-energy component. In the background, the model is tested against the Supernova type Ia (SNIa) data of the Constitution set and on the perturbative level against growth rate data, among them those of the WiggleZ survey, and the data of the 2dFGRS project. Our results indicate that a transient phase of accelerated expansion is not excluded by current observations.

  15. Uniform acceleration in general relativity

    NASA Astrophysics Data System (ADS)

    Friedman, Yaakov; Scarr, Tzvi

    2015-10-01

    We extend de la Fuente and Romero's (Gen Relativ Gravit 47:33, 2015) defining equation for uniform acceleration in a general curved spacetime from linear acceleration to the full Lorentz covariant uniform acceleration. In a flat spacetime background, we have explicit solutions. We use generalized Fermi-Walker transport to parallel transport the Frenet basis along the trajectory. In flat spacetime, we obtain velocity and acceleration transformations from a uniformly accelerated system to an inertial system. We obtain the time dilation between accelerated clocks. We apply our acceleration transformations to the motion of a charged particle in a constant electromagnetic field and recover the Lorentz-Abraham-Dirac equation.

  16. Microelectromechanical acceleration-sensing apparatus

    DOEpatents

    Lee, Robb M.; Shul, Randy J.; Polosky, Marc A.; Hoke, Darren A.; Vernon, George E.

    2006-12-12

    An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

  17. Diffusive Shock Acceleration

    NASA Astrophysics Data System (ADS)

    Baring, Matthew

    2003-04-01

    The process of diffusive acceleration of charged particles in shocked plasmas is widely invoked in astrophysics to account for the ubiquitous presence of signatures of non-thermal relativistic electrons and ions in the universe. This statistical energization mechanism, manifested in turbulent media, was first posited by Enrico Fermi in 1949 to explain the observed cosmic ray population, which exhibits an almost power-law distribution in rigidity. The absence of a momentum scale is a key characteristic of diffusive shock acceleration, and astrophysical systems generally only impose scales at the injection (low energy) and loss (high energy) ends of the particle spectrum. The existence of structure in the cosmic ray spectrum (the "knee") at around 3000 TeV has promoted contentions that there are at least two origins for cosmic rays, a galactic one supplying those up to the knee, and perhaps an extragalactic one that can explain even the ultra-high energy cosmic rays (UHECRs) seen at 1-300 EeV. Accounting for the UHECRs with familiar astrophysical sites of acceleration has historically proven difficult due to the need to assume high magnetic fields in order to reduce the shortest diffusive acceleration timescale, the ion gyroperiod, to meaningful values. Yet active galaxies and gamma-ray bursts remain strong and interesting candidate sources for UHECRs, turning the theoretical focus to relativistic shocks. This review summarizes properties of diffusive shock acceleration that are salient to the issue of UHECR generation. These include spectral indices, anisotropies, acceleration efficencies and timescales, as functions of the shock speed and mean field orientation, and also the degree of field turbulence. Astrophysical sites for UHECR production are also critiqued.

  18. 'Light Sail' Acceleration Reexamined

    SciTech Connect

    Macchi, Andrea; Veghini, Silvia; Pegoraro, Francesco

    2009-08-21

    The dynamics of the acceleration of ultrathin foil targets by the radiation pressure of superintense, circularly polarized laser pulses is investigated by analytical modeling and particle-in-cell simulations. By addressing self-induced transparency and charge separation effects, it is shown that for 'optimal' values of the foil thickness only a thin layer at the rear side is accelerated by radiation pressure. The simple 'light sail' model gives a good estimate of the energy per nucleon, but overestimates the conversion efficiency of laser energy into monoenergetic ions.

  19. HIGH GRADIENT INDUCTION ACCELERATOR

    SciTech Connect

    Caporaso, G J; Sampayan, S; Chen, Y; Blackfield, D; Harris, J; Hawkins, S; Holmes, C; Krogh, M; Nelson, S; Nunnally, W; Paul, A; Poole, B; Rhodes, M; Sanders, D; Selenes, K; Sullivan, J; Wang, L; Watson, J

    2007-06-21

    A new type of compact induction accelerator is under development at the Lawrence Livermore National Laboratory that promises to increase the average accelerating gradient by at least an order of magnitude over that of existing induction machines. The machine is based on the use of high gradient vacuum insulators, advanced dielectric materials and switches and is stimulated by the desire for compact flash x-ray radiography sources. Research describing an extreme variant of this technology aimed at proton therapy for cancer will be described. Progress in applying this technology to several applications will be reviewed.

  20. "Light sail" acceleration reexamined.

    PubMed

    Macchi, Andrea; Veghini, Silvia; Pegoraro, Francesco

    2009-08-21

    The dynamics of the acceleration of ultrathin foil targets by the radiation pressure of superintense, circularly polarized laser pulses is investigated by analytical modeling and particle-in-cell simulations. By addressing self-induced transparency and charge separation effects, it is shown that for "optimal" values of the foil thickness only a thin layer at the rear side is accelerated by radiation pressure. The simple "light sail" model gives a good estimate of the energy per nucleon, but overestimates the conversion efficiency of laser energy into monoenergetic ions.

  1. High intensity hadron accelerators

    SciTech Connect

    Teng, L.C.

    1989-05-01

    This rapporteur report consists mainly of two parts. Part I is an abridged review of the status of all High Intensity Hadron Accelerator projects in the world in semi-tabulated form for quick reference and comparison. Part II is a brief discussion of the salient features of the different technologies involved. The discussion is based mainly on my personal experiences and opinions, tempered, I hope, by the discussions I participated in in the various parallel sessions of the workshop. In addition, appended at the end is my evaluation and expression of the merits of high intensity hadron accelerators as research facilities for nuclear and particle physics.

  2. [Echocardiography in mouse].

    PubMed

    Fayssoil, A

    2008-06-01

    Assessing cardiac phenotype requires invasive or noninvasive techniques in mouse. Echocardiography is a noninvasive technique for evaluating cardiac function. The purpose of this paper is to underline echocardiography modalities and new tools Doppler applications like tissue Doppler imaging.

  3. Mouse Activity across Time Scales: Fractal Scenarios

    PubMed Central

    Lima, G. Z. dos Santos; Lobão-Soares, B.; do Nascimento, G. C.; França, Arthur S. C.; Muratori, L.; Ribeiro, S.; Corso, G.

    2014-01-01

    In this work we devise a classification of mouse activity patterns based on accelerometer data using Detrended Fluctuation Analysis. We use two characteristic mouse behavioural states as benchmarks in this study: waking in free activity and slow-wave sleep (SWS). In both situations we find roughly the same pattern: for short time intervals we observe high correlation in activity - a typical 1/f complex pattern - while for large time intervals there is anti-correlation. High correlation of short intervals ( to : waking state and to : SWS) is related to highly coordinated muscle activity. In the waking state we associate high correlation both to muscle activity and to mouse stereotyped movements (grooming, waking, etc.). On the other side, the observed anti-correlation over large time scales ( to : waking state and to : SWS) during SWS appears related to a feedback autonomic response. The transition from correlated regime at short scales to an anti-correlated regime at large scales during SWS is given by the respiratory cycle interval, while during the waking state this transition occurs at the time scale corresponding to the duration of the stereotyped mouse movements. Furthermore, we find that the waking state is characterized by longer time scales than SWS and by a softer transition from correlation to anti-correlation. Moreover, this soft transition in the waking state encompass a behavioural time scale window that gives rise to a multifractal pattern. We believe that the observed multifractality in mouse activity is formed by the integration of several stereotyped movements each one with a characteristic time correlation. Finally, we compare scaling properties of body acceleration fluctuation time series during sleep and wake periods for healthy mice. Interestingly, differences between sleep and wake in the scaling exponents are comparable to previous works regarding human heartbeat. Complementarily, the nature of these sleep-wake dynamics could lead to a better

  4. Mouse Cleaning Apparatus and Method

    NASA Technical Reports Server (NTRS)

    Williams, Glenn L. (Inventor)

    2005-01-01

    The method of using the mouse pad cleaning apparatus is disclosed and claimed. The method comprises the steps of uncovering the mouse cleaning surface, applying the mouse and ball of the mouse to the cleaning surface, moving the mouse in a rotational pattern on the mouse cleaning surface, removing the mouse form the mouse cleaning surface, washing the cleaning surface, and covering the mouse cleaning surface. A mouse pad cleaning apparatus comprising a plurality of substrates, each said substrate having adhesive thereon, said plurality of substrates residing in and affixed to a receptacle. A single substrate having adhesive, which may be washable or non-washable, thereon may be employed. The washable adhesive may be an organopolysiloxane or gelatinous elastomer.

  5. Mechanisms of aging in senescence-accelerated mice

    PubMed Central

    Carter, Todd A; Greenhall, Jennifer A; Yoshida, Shigeo; Fuchs, Sebastian; Helton, Robert; Swaroop, Anand; Lockhart, David J; Barlow, Carrolee

    2005-01-01

    Background Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J). Results The majority of age-related gene expression changes were strain-specific, with only a few common pathways found for normal and accelerated neurological aging. Polymorphism screening led to the identification of mutations that could have a direct impact on important disease processes, including a mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic expression of the gene for the chemokine CCL19, which is involved in the inflammatory response. Conclusion We show that combining the study of inbred mouse strains with interesting traits and gene-expression profiling can lead to the discovery of genes important for complex phenotypes. Furthermore, full-genome polymorphism detection, sequencing and gene-expression profiling of inbred mouse strains with interesting phenotypic differences may provide unique insights into the molecular genetics of late-manifesting complex diseases. PMID:15960800

  6. Does targeted pre-load optimisation by stroke volume variation attenuate a reduction in cardiac output in the prone position.

    PubMed

    Wu, C-Y; Lee, T-S; Chan, K-C; Jeng, C-S; Cheng, Y-J

    2012-07-01

    The prone position can reduce cardiac output by up to 25% due to reduced preload. We hypothesised that preload optimisation targeted to stroke volume variation before turning prone might alleviate this. A supine threshold stroke volume variation of 14% in a preliminary study identified patients whose cardiac outputs would decline when turned prone. In 45 patients, cardiac output declined only in the group whose supine stroke volume variation was high (mean (SD) 5.1 (2.0) to 3.9 (1.9) l.min(-1) ; p < 0.001), but not in patients in whom it was low, or in those in whom stroke volume variation was high, but who received volume preload (p = 0.525 and 0.941, respectively). We conclude that targeted preload optimisation using a supine stroke volume variation value < 14% is effective in preventing falls in cardiac output induced by the prone position.

  7. Radioisotope Dating with Accelerators.

    ERIC Educational Resources Information Center

    Muller, Richard A.

    1979-01-01

    Explains a new method of detecting radioactive isotopes by counting their accelerated ions rather than the atoms that decay during the counting period. This method increases the sensitivity by several orders of magnitude, and allows one to find the ages of much older and smaller samples. (GA)

  8. Accelerated Management Development

    ERIC Educational Resources Information Center

    Munn, Kenn

    1974-01-01

    Western Electric's accelerated management development program for hand picked college graduate students consists of a high risk training project in which the management candidate accomplishes his task or is terminated. The success of such projects puts candidates in third level management in seven years or half the normal time. (DS)

  9. FPGA Verification Accelerator (FVAX)

    NASA Technical Reports Server (NTRS)

    Oh, Jane; Burke, Gary

    2008-01-01

    Is Verification Acceleration Possible? - Increasing the visibility of the internal nodes of the FPGA results in much faster debug time - Forcing internal signals directly allows a problem condition to be setup very quickly center dot Is this all? - No, this is part of a comprehensive effort to improve the JPL FPGA design and V&V process.

  10. Combined generating-accelerating buncher for compact linear accelerators

    NASA Astrophysics Data System (ADS)

    Savin, E. A.; Matsievskiy, S. V.; Sobenin, N. P.; Sokolov, I. D.; Zavadtsev, A. A.

    2016-09-01

    Described in the previous article [1] method of the power extraction from the modulated electron beam has been applied to the compact standing wave electron linear accelerator feeding system, which doesnt require any connection waveguides between the power source and the accelerator itself [2]. Generating and accelerating bunches meet in the hybrid accelerating cell operating at TM020 mode, thus the accelerating module is placed on the axis of the generating module, which consists from the pulsed high voltage electron sources and electrons dumps. This combination makes the accelerator very compact in size which is very valuable for the modern applications such as portable inspection sources. Simulations and geometry cold tests are presented.

  11. Inhibition of adenosine metabolism induces changes in post-ictal depression, respiration, and mortality in genetically epilepsy prone rats.

    PubMed

    Kommajosyula, Srinivasa P; Randall, Marcus E; Faingold, Carl L

    2016-01-01

    A major cause of mortality in epilepsy patients is sudden unexpected death in epilepsy (SUDEP). Post-ictal respiratory dysfunction following generalized convulsive seizures is most commonly observed in witnessed cases of human SUDEP. DBA mouse models of SUDEP are induced by audiogenic seizures (AGSz) and show high incidences of seizure-induced death due to respiratory depression. The relatively low incidence of human SUDEP suggests that it may be useful to examine seizure-associated death in an AGSz model that rarely exhibits sudden death, such as genetically epilepsy-prone rats (GEPR-9s). Adenosine is released extensively during seizures and depresses respiration, which may contribute to seizure-induced death. The present study examined the effects of inhibiting adenosine metabolism on the durations of post-ictal depression (PID) and respiratory distress (RD), changes in blood oxygen saturation (% SpO2), and the incidence of post-seizure mortality in GEPR-9s. Systemic administration of adenosine metabolism inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, 30 mg/kg) with 5-Iodotubericidin (5-ITU, 3mg/kg) in GEPR-9s resulted in significant changes in the duration of AGSz-induced PID as compared to vehicle in both genders. These agents also significantly increased the duration of post-seizure RD and significantly decreased the mean% SpO2 after AGSz, as compared to vehicle but only in females. Subsequently, we observed that the incidences of death in both genders 12-48 h post-seizure were significantly greater in drug vs. vehicle treatment. The incidence of death in females was also significantly higher than in males, which is consistent with the elevated seizure sensitivity of female GEPR-9s developmentally. These results support a potentially important role of elevated adenosine levels following generalized seizures in the increased incidence of death in GEPR-9s induced by adenosine metabolism inhibitors. These findings may also be relevant to human SUDEP, in

  12. Smartphone addiction proneness in relation to sleep and morningness–eveningness in German adolescents

    PubMed Central

    Randler, Christoph; Wolfgang, Lucia; Matt, Katharina; Demirhan, Eda; Horzum, Mehmet Barış; Beşoluk, Şenol

    2016-01-01

    Background Mobile phones are an important part of adolescents’ life. In this study, the relationships among smartphone addiction, age, gender, and chronotype of German adolescents were examined. Materials and methods Two studies focused on two different measures of smartphone addiction. The Smartphone Addiction Proneness Scale (SAPS) was applied to 342 younger adolescents (13.39 ± 1.77; 176 boys, 165 girls, and 1 not indicated) in Study 1 and the Smartphone Addiction Scale was applied to 208 older adolescents (17.07 ± 4.28; 146 girls and 62 boys) in Study 2, both samples in southwest Germany. In addition, a demographic questionnaire and the Composite Scale of Morningness (CSM) and sleep measures were implemented. Results The most remarkable result of this study was that morningness–eveningness (as measured by CSM scores) is an important predictor for smartphone addiction; even stronger than sleep duration. Evening oriented adolescents scored higher on both smartphone addiction scales. In addition, gender is an important predictor for smartphone addiction and girls are more prone to become addicted. In addition, while sleep duration on weekdays negatively predicted SAPS, age, sleep duration on weekends, and midpoint of sleep on weekdays and weekends did not predicted smartphone addiction in both scales. The analysis of covariance revealed statistically significant effects of the covariates gender and age in both studies, as well as the main effect of chronotype. According to the t-test results, girls had higher scores than boys in smartphone addiction. Conclusion Evening types and girls are more prone to become smartphone addicted. PMID:27499228

  13. Influence Of Scapular Position On The Core Musculature Activation In The Prone Plank Exercise.

    PubMed

    Cortell-Tormo, Juan M; García-Jaén, Miguel; Chulvi-Medrano, Iván; Hernández-Sánchez, Sergio; Lucas-Cuevas, Ángel G; Tortosa-Martínez, Juan

    2016-10-26

    Prone plank is a widely used exercise in core stability training. Research has shown that pelvic tilt plays an important role on the electromyographical (EMG) activation of core musculature. However, the influence of scapular position on EMG activation is currently unknown. Therefore, this study evaluated the influence of scapular position on the core muscles during a prone plank. Surface electromyography of the rectus abdominis (RA), external oblique (EO), internal oblique (IO) and erector spinae (ES) was collected in fifteen participants (10 men, 5 women). Four variations of the prone plank were evaluated: scapular abduction with anterior (ABANT) and posterior (ABRET) pelvic tilt; and scapular adduction with anterior (ADANT) and posterior (ADRET) pelvic tilt. Individual muscle EMG and overall EMG for each plank exercise was analyzed. Joint positions were controlled with a 2D kinematic analysis. Ratings of perceived effort (RPE) were also registered. ADRET resulted in higher overall EMG activity compared to ABANT (p=0.04) and ADANT (p=0.04). Moreover, ADRET resulted in greater EMG activity compared to ADANT, ABANT, and ABRET for EO (p=0.000; p=0.000; p=0.035), IO (p=0.000; p=0.000; p=0.005) and ES (p=0.019; p=0.001; p=0.014). Regarding RA, ADRET was significantly higher compared to ADANT (p=0.002) and ABANT (p=0.005). Finally, ADRET provoked a higher RPE compared to ABANT (p=0.000), ABRET (p=0.001) and ADANT (p=0.015). These findings demonstrate the influence of the scapular and pelvic position on the EMG response of the core muscle groups analyzed in this study, and highlight the greater contribution of these muscles to the postural stabilizing demands during posterior pelvic tilt positions, particularly when the scapulae are in adduction.

  14. On the retention of gene duplicates prone to dominant deleterious mutations.

    PubMed

    Malaguti, Giulia; Singh, Param Priya; Isambert, Hervé

    2014-05-01

    Recent studies have shown that gene families from different functional categories have been preferentially expanded either by small scale duplication (SSD) or by whole-genome duplication (WGD). In particular, gene families prone to dominant deleterious mutations and implicated in cancers and other genetic diseases in human have been greatly expanded through two rounds of WGD dating back from early vertebrates. Here, we strengthen this intriguing observation, showing that human oncogenes involved in different primary tumors have retained many WGD duplicates compared to other human genes. In order to rationalize this evolutionary outcome, we propose a consistent population genetics model to analyze the retention of SSD and WGD duplicates taking into account their propensity to acquire dominant deleterious mutations. We solve a deterministic haploid model including initial duplicated loci, their retention through sub-functionalization or their neutral loss-of-function or deleterious gain-of-function at one locus. Extensions to diploid genotypes are presented and population size effects are analyzed using stochastic simulations. The only difference between the SSD and WGD scenarios is the initial number of individuals with duplicated loci. While SSD duplicates need to spread through the entire population from a single individual to reach fixation, WGD duplicates are de facto fixed in the small initial post-WGD population arising through the ploidy incompatibility between post-WGD individuals and the rest of the pre-WGD population. WGD duplicates prone to dominant deleterious mutations are then shown to be indirectly selected through purifying selection in post-WGD species, whereas SSD duplicates typically require positive selection. These results highlight the long-term evolution mechanisms behind the surprising accumulation of WGD duplicates prone to dominant deleterious mutations and are shown to be consistent with cancer genome data on the prevalence of human

  15. Quick Analysis Method for Estimating Debris Flow Prone Area Caused by Overflow from Landslide dam

    NASA Astrophysics Data System (ADS)

    Shimizu, T.; Uchida, T.; Yamakoshi, T.; Yoshino, K.; Kisa, H.; Ishizuka, T.; Kaji, A.

    2012-04-01

    When earthquake or torrential rainfall cause deep catastrophic landslides, landslide dams can be formed in mountainous region. If water overflows from the landslide dams, large scale debris flow can occurs and possibly causes serious disasters in the downward region. Debris flow caused by the overflow from landslide dam is possible to affect the larger area than normal debris flow and flash flood. It is important for both a decision maker and resident in the area to recognize the disaster prone area as early as possible. For that reason, it is important to establish a quick analysis method for estimating debris flow prone area caused by overflow from landslide dams under the emergency situation. This situation requires the method to have both accuracy and speed for release. Nonetheless these two factors have trade-off relationship. We recently developed the quick analysis method to estimate debris flow disaster prone area caused by overflow from landslide dams. The method including the ways of efficient survey and numerical simulation programs called QUAD-L (QUick Analysis system for Debris flow caused by Landslide dam overflow). Our quick analysis system was actually applied to show the area for evacuation against debris flow caused by overflow from landslide dam formed by the 2011 Typhoon Talas which hit mainly the central region of Japan on September 2-4th, 2011. In addition to background of this application, since May 1st, 2011, Erosion and Sediment Control (SABO) Department of the Ministry of Land, Infrastructure, Transport and Tourism, Japan (MLIT) launched a new scheme using above-mentioned quick analysis method.

  16. Smartphone addiction proneness in relation to sleep and morningness-eveningness in German adolescents.

    PubMed

    Randler, Christoph; Wolfgang, Lucia; Matt, Katharina; Demirhan, Eda; Horzum, Mehmet Barış; Beşoluk, Şenol

    2016-09-01

    Background Mobile phones are an important part of adolescents' life. In this study, the relationships among smartphone addiction, age, gender, and chronotype of German adolescents were examined. Materials and methods Two studies focused on two different measures of smartphone addiction. The Smartphone Addiction Proneness Scale (SAPS) was applied to 342 younger adolescents (13.39 ± 1.77; 176 boys, 165 girls, and 1 not indicated) in Study 1 and the Smartphone Addiction Scale was applied to 208 older adolescents (17.07 ± 4.28; 146 girls and 62 boys) in Study 2, both samples in southwest Germany. In addition, a demographic questionnaire and the Composite Scale of Morningness (CSM) and sleep measures were implemented. Results The most remarkable result of this study was that morningness-eveningness (as measured by CSM scores) is an important predictor for smartphone addiction; even stronger than sleep duration. Evening oriented adolescents scored higher on both smartphone addiction scales. In addition, gender is an important predictor for smartphone addiction and girls are more prone to become addicted. In addition, while sleep duration on weekdays negatively predicted SAPS, age, sleep duration on weekends, and midpoint of sleep on weekdays and weekends did not predicted smartphone addiction in both scales. The analysis of covariance revealed statistically significant effects of the covariates gender and age in both studies, as well as the main effect of chronotype. According to the t-test results, girls had higher scores than boys in smartphone addiction. Conclusion Evening types and girls are more prone to become smartphone addicted.

  17. The contact allergen dinitrochlorobenzene (DNCB) and respiratory allergy in the Th2-prone Brown Norway rat.

    PubMed

    Kuper, C Frieke; Stierum, Rob H; Boorsma, Andre; Schijf, Marcel A; Prinsen, Menk; Bruijntjes, Joost P; Bloksma, Nanne; Arts, Josje H E

    2008-04-18

    All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%, day 7) and a head/nose-only inhalation challenge of 27mg/m3 of DNCB (15 min, day 21), using a protocol that successfully identified chemical respiratory allergens. Skin allergy to DNCB was examined in BN rats and Th1-prone Wistar rats in a local lymph node assay followed by a topical patch challenge of 0.1% DNCB. Sensitization of BN rats via the skin induced DNCB-specific IgG in serum, but not in all animals, and an increased number of CD4+ cells in the lung parenchyma. Subsequent inhalation challenge with DNCB did not provoke apneas or allergic inflammation (signs of respiratory allergy) in the BN rats. However, microarray analysis of mRNA isolated from the lung revealed upregulation of the genes for Ccl2 (MCP-1), Ccl4 (MIP-1beta), Ccl7 and Ccl17. Skin challenge induced considerably less skin irritation and allergic dermatitis in the BN rat than in the Wistar rat. In conclusion, the Th2-prone BN rat appeared less sensitive to DNCB than the Wistar rat; nevertheless, DNCB induced allergic inflammation in the skin of BN rats but even a relatively high challenge concentration did not induce allergy in the respiratory tract, although genes associated with allergy were upregulated in lung tissue.

  18. Nanomaterial Containing Wall Paints Can Increase Radon Concentration in Houses Located in Radon Prone Areas

    PubMed Central

    Haghani, M.; Mortazavi, S. M. J.; Faghihi, R.; Mehdizadeh, S.; Moradgholi, J.; Darvish, L.; Fathi-Pour, E.; Ansari, L.; Ghanbar-pour, M. R.

    2013-01-01

    Background: Nowadays, extensive technological advancements have made it possible to use nanopaints which show exciting properties. In IR Iran excessive radon levels (up to 3700 Bq m–3) have been reported in homes located in radon prone areas. Over the past decades, concerns have been raised about the risk posed by residential radon exposure. Objective: This study aims at investigating the effect of using nanomaterial containing wall paints on radon concentration in homes. Methods: Two wooden model houses were used in this study. Soil samples from Ramsar high background radiation areas were used for simulating the situation of a typical house in radon-prone areas. Conventional water-soluble wall paint was used for painting the walls of the 1st house model; while the 2nd house model was painted with the same wall paint with montmorillonitenanoclay. Results: Three days after sealing the house models, radon level was measured by using a portable radon survey meter. The mean radon level inside the 1st house model (conventional paint) was 515.3 ± 17.8 Bq/m3 while the mean radon concentration in the 2nd house model (nano-painted house model) was 570.8 ± 18.5 Bq/m3. The difference between these means was statistically significant (P<0.001). Conclusion: To the best of our knowledge, this study is the first investigation on the effect of nano-material containing wall paints on indoor radon concentrations.  It can be concluded that nano-material-containing wall paints should not be used in houses with wooden walls located in radon prone areas. Although the mechanism of this effect is not clearly known, decreased porosity in nano-paints might be a key factor in increasing the radon concentration in homes. PMID:25505754

  19. The volume effect in irradiated mouse colorectum

    NASA Astrophysics Data System (ADS)

    Skwarchuk, Mark William

    1997-11-01

    Damage of the colorectum is the dose-limiting normal tissue complication following radiotherapy of prostate and cervical cancers. One approach for decreasing complications is to physically reduce the treatment volume. Mathematical models have been previously developed to describe the change in associated toxicity with a change in irradiated volume, i.e. the 'volume effect', for serial-type normal tissues including the colorectum. The first goal of this thesis was to test the hypothesis that there would not be a threshold length in the development of obstruction after irradiation of mouse colorectum, as predicted by the Probability model of the volume effect. The second goal was to examine if there were differences in the threshold and in the incidence of colorectal obstruction after irradiation of two mouse strains, C57B1/6 (C57) and C3Hf/Kam (C3H), previously found to be fibrosis-prone and-resistant, respectively, after lung irradiation due, in part, to genetic differences. The hypothesis examined was that differences in incidence between strains were due to the differential expression of the fibrogenic cytokines TGF/beta and TNF/alpha. Various lengths of C57 and C3H mouse colorectum were irradiated and the incidence of colorectal obstruction was followed up to 15 months. A threshold length was observed for both mouse strains, in contradiction of model predictions. The mechanism of the threshold was epithelial regeneration after irradiation. C57 mice had significantly higher incidence of colorectal obstruction compared to C3H mice, especially at smaller irradiated lengths. Colorectal tissue was obtained at various times after irradiation and prepared for histology, immunohistochemistry and RNase protection assay for measurement of TGF/beta 1, 2, 3 and TNF/alpha mRNA. Distinct strain differences in the histological time of appearance and spatial locations of fibrosis were observed. However, there were no consistent strain difference in mRNA levels or

  20. Neurodegeneration in accelerated aging.

    PubMed

    Scheibye-Knudsen, Moren

    2016-11-01

    The growing proportion of elderly people represents an increasing economic burden, not least because of age-associated diseases that pose a significant cost to the health service. Finding possible interventions to age-associated disorders therefore have wide ranging implications. A number of genetically defined accelerated aging diseases have been characterized that can aid in our understanding of aging. Interestingly, all these diseases are associated with defects in the maintenance of our genome. A subset of these disorders, Cockayne syndrome, Xeroderma pigmentosum group A and ataxia-telangiectasia, show neurological involvement reminiscent of what is seen in primary human mitochondrial diseases. Mitochondria are the power plants of the cells converting energy stored in oxygen, sugar, fat, and protein into ATP, the energetic currency of our body. Emerging evidence has linked this organelle to aging and finding mitochondrial dysfunction in accelerated aging disorders thereby strengthens the mitochondrial theory of aging. This theory states that an accumulation of damage to the mitochondria may underlie the process of aging. Indeed, it appears that some accelerated aging disorders that show neurodegeneration also have mitochondrial dysfunction. The mitochondrial alterations may be secondary to defects in nuclear DNA repair. Indeed, nuclear DNA damage may lead to increased energy consumption, alterations in mitochondrial ATP production and defects in mitochondrial recycling, a term called mitophagy. These changes may be caused by activation of poly-ADP-ribose-polymerase 1 (PARP1), an enzyme that responds to DNA damage. Upon activation PARP1 utilizes key metabolites that attenuate pathways that are normally protective for the cell. Notably, pharmacological inhibition of PARP1 or reconstitution of the metabolites rescues the changes caused by PARP1 hyperactivation and in many cases reverse the phenotypes associated with accelerated aging. This implies that modulation

  1. Menopause accelerates biological aging

    PubMed Central

    Levine, Morgan E.; Lu, Ake T.; Chen, Brian H.; Hernandez, Dena G.; Singleton, Andrew B.; Ferrucci, Luigi; Bandinelli, Stefania; Salfati, Elias; Manson, JoAnn E.; Quach, Austin; Kusters, Cynthia D. J.; Kuh, Diana; Wong, Andrew; Teschendorff, Andrew E.; Widschwendter, Martin; Ritz, Beate R.; Absher, Devin; Assimes, Themistocles L.; Horvath, Steve

    2016-01-01

    Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further. PMID:27457926

  2. Excessive daydreaming: a case history and discussion of mind wandering and high fantasy proneness.

    PubMed

    Schupak, Cynthia; Rosenthal, Jesse

    2009-03-01

    This case study describes a patient presenting with a long history of excessive daydreaming which has caused her distress but is not incident to any other apparent clinical psychiatric disorders. We have treated this patient for over 10 years, and she has responded favorably to fluvoxamine therapy, stating that it helps to control her daydreaming. Our patient, and other psychotherpists, have brought to our attention other possible cases of excessive daydreaming. We examine the available literature regarding daydreaming, mind wandering, and fantasy proneness relative to current cognitive and neuroanatomical models of executive attention.

  3. Correlates of the multidimensional construct of hypnotizability: paranormal belief, fantasy proneness, magical ideation, and dissociation.

    PubMed

    Dasse, Michelle N; Elkins, Gary R; Weaver, Charles A

    2015-01-01

    Hypnotizability is a multifaceted construct that may relate to multiple aspects of personality and beliefs. This study sought to address 4 known correlates of hypnotizability to aid in its understanding. Eighty undergraduates completed the Magical Ideation Scale (MIS), the Creative Experiences Questionnaire (CEQ), the Australian Sheep-Goat Scale (ASGS), and the Dissociative Experiences Scale (DES) and then were administered the Creative Imagination Scale (CIS). All 5 scales were significantly correlated. Participants higher in hypnotizability scored higher on the CEQ and the MIS. The findings demonstrate the influence of fantasy proneness and magical thinking on hypnotizability and support the theory that hypnotizability is a complex interaction of multiple traits.

  4. Crisis Management of Accidental Extubation in a Prone-Positioned Patient with Klippel-Feil Syndrome.

    PubMed

    Spond, Matthew; Burns, Tyler; Rosenbaum, Thea; Lienhart, Kristen

    2016-06-15

    We present the case of an accidental extubation in a prone-positioned patient with a challenging airway because of Klippel-Feil syndrome and previous cervical spine fusions. The surgical procedure was well underway when this occurred, which added substantially to the difficulties produced by this event. We herein highlight the corrective steps we took in our case. We also recommend the need for a comprehensive preoperative briefing with all operating room personnel together with an action plan for how to prevent this particular scenario.

  5. Short-term absence from industry: III The inference of `proneness' and a search for causes

    PubMed Central

    Froggatt, P.

    1970-01-01

    Froggatt, P. (1970).Brit. J. industr. Med.,27, 297-312. Short-term absence from industry. III. The inference of `proneness' and a search for causes. The abilities of five hypotheses (`chance', `proneness', and three of `true contagion' - as defined in the text) to explain the distributions of one-day and two-day absences among groups of male and female industrial personnel and clerks in government service are examined by curve-fitting and correlation methods. The five hypotheses generate (in order) the Poisson, negative binomial, Neyman type A, Short, and Hermite (two-parameter form) distributions which are fitted to the data using maximum-likelihood estimates. The conclusion is drawn that `proneness', i.e., a stable `liability', compounded from several though unquantifiable factors, and constant for each individual over the period of the study, is markedly successful in explaining the data. It is emphasized that some of the other hypotheses under test cannot be unequivocably rejected; and there is in theory an infinite number, still unformulated or untested, which may be acceptable or even fit the data better. Correlation coefficients for the numbers of one-day (and two-day) absences taken by the same individuals in two equal non-overlapping periods of time are of the order 0·5 to 0·7 (0·3 to 0·5 for two-day absences) and the corresponding regressions fulfil linear requirements. These correlations are higher than any between `personal characteristics' and their overt consequence in contingent fields of human enquiry. For one-day absences the predictive power for the future from the past record could in some circumstances justify executive action. When freely available, overtime was greatest among junior married men and least among junior married women. The validity of the inference of `proneness' and the implications of its acceptance are fully discussed. While interpretation is not unequivocal, one-day absences seemingly have many causes; two-day absences are

  6. On the relationship between meaning in life and boredom proneness: examining a logotherapy postulate.

    PubMed

    Melton, Amanda M A; Schulenberg, Stefan E

    2007-12-01

    Logotherapy, developed by Viktor Frankl, posits that when one lacks meaning in life, boredom can result. Thus, the two constructs should be inversely related. To examine this relationship, 279 students (M = 19.8 yr., SD = 2.6; 179 women, 98 men) from a university in the southern United States were administered the Purpose of Life test and the Boredom Proneness Scale. As expected, a statistically significant negative correlation was found between the scores on the two scales (r = -.71). Directions for research are offered.

  7. Holding Back the Tears: Individual Differences in Adult Crying Proneness Reflect Attachment Orientation and Attitudes to Crying.

    PubMed

    Millings, Abigail; Hepper, Erica G; Hart, Claire M; Swift, Louise; Rowe, Angela C

    2016-01-01

    Despite being a universal human attachment behavior, little is known about individual differences in crying. To facilitate such examination we first recommend shortened versions of the attitudes and proneness sections of the Adult Crying Inventory using two independent samples. Importantly, we examine attachment orientation differences in crying proneness and test the mediating role of attitudes toward crying in this relationship. Participants (Sample 1 N = 623, Sample 2 N = 781), completed online measures of adult attachment dimensions (avoidance and anxiety), attitudes toward crying, and crying proneness. Exploratory factor analyses in Sample 1 revealed four factors for crying attitudes: crying helps one feel better; crying is healthy; hatred of crying; and crying is controllable; and three factors for crying proneness: threat to self; sadness; and joy. Confirmatory factor analyses in Sample 2 replicated these structures. Theoretically and statistically justified short forms of each scale were created. Multiple mediation analyses revealed similar patterns of results across the two samples, with the attitudes "crying is healthy" and "crying is controllable" consistently mediating the positive links between attachment anxiety and crying proneness, and the negative links between attachment avoidance and crying proneness. Results are discussed in relation to attachment and emotion regulation literature.

  8. Holding Back the Tears: Individual Differences in Adult Crying Proneness Reflect Attachment Orientation and Attitudes to Crying

    PubMed Central

    Millings, Abigail; Hepper, Erica G.; Hart, Claire M.; Swift, Louise; Rowe, Angela C.

    2016-01-01

    Despite being a universal human attachment behavior, little is known about individual differences in crying. To facilitate such examination we first recommend shortened versions of the attitudes and proneness sections of the Adult Crying Inventory using two independent samples. Importantly, we examine attachment orientation differences in crying proneness and test the mediating role of attitudes toward crying in this relationship. Participants (Sample 1 N = 623, Sample 2 N = 781), completed online measures of adult attachment dimensions (avoidance and anxiety), attitudes toward crying, and crying proneness. Exploratory factor analyses in Sample 1 revealed four factors for crying attitudes: crying helps one feel better; crying is healthy; hatred of crying; and crying is controllable; and three factors for crying proneness: threat to self; sadness; and joy. Confirmatory factor analyses in Sample 2 replicated these structures. Theoretically and statistically justified short forms of each scale were created. Multiple mediation analyses revealed similar patterns of results across the two samples, with the attitudes “crying is healthy” and “crying is controllable” consistently mediating the positive links between attachment anxiety and crying proneness, and the negative links between attachment avoidance and crying proneness. Results are discussed in relation to attachment and emotion regulation literature. PMID:27458402

  9. Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies

    SciTech Connect

    Williams, Jason M.; Rani, Sudheer D.; Li, Xia; Whisenant, Jennifer G.; Abramson, Richard G.; Arlinghaus, Lori R.; Lee, Tzu-Cheng; MacDonald, Lawrence R.; Partridge, Savannah C.; Kang, Hakmook; Linden, Hannah M.; Kinahan, Paul E.; Yankeelov, Thomas E.

    2015-07-15

    Purpose: Previous studies have demonstrated how imaging of the breast with patients lying prone using a supportive positioning device markedly facilitates longitudinal and/or multimodal image registration. In this contribution, the authors’ primary objective was to determine if there are differences in the standardized uptake value (SUV) derived from [{sup 18}F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in breast tumors imaged in the standard supine position and in the prone position using a specialized positioning device. Methods: A custom positioning device was constructed to allow for breast scanning in the prone position. Rigid and nonrigid phantom studies evaluated differences in prone and supine PET. Clinical studies comprised 18F-FDG-PET of 34 patients with locally advanced breast cancer imaged in the prone position (with the custom support) followed by imaging in the supine position (without the support). Mean and maximum values (SUV{sub peak} and SUV{sub max}, respectively) were obtained from tumor regions-of-interest for both positions. Prone and supine SUV were linearly corrected to account for the differences in 18F-FDG uptake time. Correlation, Bland–Altman, and nonparametric analyses were performed on uptake time-corrected and uncorrected data. Results: SUV from the rigid PET breast phantom imaged in the prone position with the support device was 1.9% lower than without the support device. In the nonrigid PET breast phantom, prone SUV with the support device was 5.0% lower than supine SUV without the support device. In patients, the median (range) difference in uptake time between prone and supine scans was 16.4 min (13.4–30.9 min), which was significantly—but not completely—reduced by the linear correction method. SUV{sub peak} and SUV{sub max} from prone versus supine scans were highly correlated, with concordance correlation coefficients of 0.91 and 0.90, respectively. Prone SUV{sub peak} and SUV{sub max} were

  10. Stacked insulator induction accelerator gaps

    SciTech Connect

    Houck, T.I.; Westenskow, G.A.; Kim, J.S.; Eylon, S.; Henestroza, E.; Yu, S.S.; Vanecek, D.

    1997-05-01

    Stacked insulators, with alternating layers of insulating material and conducting film, have been shown to support high surface electrical field stresses. We have investigated the application of the stacked insulator technology to the design of induction accelerator modules for the Relativistic-Klystron Two-Beam Accelerator program. The rf properties of the accelerating gaps using stacked insulators, particularly the impedance at frequencies above the beam pipe cutoff frequency, are investigated. Low impedance is critical for Relativistic-Klystron Two-Beam Accelerator applications where a high current, bunched beam is trsnsported through many accelerating gaps. An induction accelerator module designs using a stacked insulator is presented.

  11. Automated accelerator controls for a 3 MV tandem Pelletron

    NASA Astrophysics Data System (ADS)

    Rathmell, R. D.; Kitchen, R. L.; Luck, T. R.; Sundquist, M. L.

    1991-05-01

    A new accelerator control system has been developed which uses a real-time, multitasking operating system running on a Motorola 68030 based microcomputer. The system includes multiple graphic and text displays and allows the operator to communicate via these displays to the accelerator, which is interfaced to CAMAC. Most accelerator parameters can be controlled using a mouse in conjunction with a single graphic display, eliminating the need to change CRT pages in order to control parameters from the source to the target. A touch screen is also available to permit a number of parameters to be at the operator's finger tips at all times. Operating parameters for a new beam and energy can be automatically set by scaling from a previously stored run. The program and database are structured to facilitate interlocking and closed loop control of parameters. The hardware configuration, structure and features of the software will be reviewed.

  12. Mass spectrometry with accelerators.

    PubMed

    Litherland, A E; Zhao, X-L; Kieser, W E

    2011-01-01

    As one in a series of articles on Canadian contributions to mass spectrometry, this review begins with an outline of the history of accelerator mass spectrometry (AMS), noting roles played by researchers at three Canadian AMS laboratories. After a description of the unique features of AMS, three examples, (14)C, (10)Be, and (129)I are given to illustrate the methods. The capabilities of mass spectrometry have been extended by the addition of atomic isobar selection, molecular isobar attenuation, further ion acceleration, followed by ion detection and ion identification at essentially zero dark current or ion flux. This has been accomplished by exploiting the techniques and accelerators of atomic and nuclear physics. In 1939, the first principles of AMS were established using a cyclotron. In 1977 the selection of isobars in the ion source was established when it was shown that the (14)N(-) ion was very unstable, or extremely difficult to create, making a tandem electrostatic accelerator highly suitable for assisting the mass spectrometric measurement of the rare long-lived radioactive isotope (14)C in the environment. This observation, together with the large attenuation of the molecular isobars (13)CH(-) and (12)CH 2(-) during tandem acceleration and the observed very low background contamination from the ion source, was found to facilitate the mass spectrometry of (14)C to at least a level of (14)C/C ~ 6 × 10(-16), the equivalent of a radiocarbon age of 60,000 years. Tandem Accelerator Mass Spectrometry, or AMS, has now made possible the accurate radiocarbon dating of milligram-sized carbon samples by ion counting as well as dating and tracing with many other long-lived radioactive isotopes such as (10)Be, (26)Al, (36)Cl, and (129)I. The difficulty of obtaining large anion currents with low electron affinities and the difficulties of isobar separation, especially for the heavier mass ions, has prompted the use of molecular anions and the search for alternative

  13. SU-E-J-227: Breathing Pattern Consistency and Reproducibility: Comparative Analysis for Supine and Prone Body Positioning

    SciTech Connect

    Laugeman, E; Weiss, E; Chen, S; Hugo, G; Rosu, M

    2014-06-01

    Purpose: Evaluate and compare the cycle-to-cycle consistency of breathing patterns and their reproducibility over the course of treatment, for supine and prone positioning. Methods: Respiratory traces from 25 patients were recorded for sequential supine/prone 4DCT scans acquired prior to treatment, and during the course of the treatment (weekly or bi-weekly). For each breathing cycle, the average(AVE), end-of-exhale(EoE) and end-of-inhale( EoI) locations were identified using in-house developed software. In addition, the mean values and variations for the above quantities were computed for each breathing trace. F-tests were used to compare the cycle-to-cycle consistency of all pairs of sequential supine and prone scans. Analysis of variances was also performed using population means for AVE, EoE and EoI to quantify differences between the reproducibility of prone and supine respiration traces over the treatment course. Results: Consistency: Cycle-to-cycle variations are less in prone than supine in the pre-treatment and during-treatment scans for AVE, EoE and EoI points, for the majority of patients (differences significant at p<0.05). The few cases where the respiratory pattern had more variability in prone appeared to be random events. Reproducibility: The reproducibility of breathing patterns (supine and prone) improved as treatment progressed, perhaps due to patients becoming more comfortable with the procedure. However, variability in supine position continued to remain significantly larger than in prone (p<0.05), as indicated by the variance analysis of population means for the pretreatment and subsequent during-treatment scans. Conclusions: Prone positioning stabilizes breathing patterns in most subjects investigated in this study. Importantly, a parallel analysis of the same group of patients revealed a tendency towards increasing motion amplitude of tumor targets in prone position regardless of their size or location; thus, the choice for body positioning

  14. Genome-wide profiling of yeast DNA:RNA hybrid prone sites with DRIP-chip.

    PubMed

    Chan, Yujia A; Aristizabal, Maria J; Lu, Phoebe Y T; Luo, Zongli; Hamza, Akil; Kobor, Michael S; Stirling, Peter C; Hieter, Philip

    2014-04-01

    DNA:RNA hybrid formation is emerging as a significant cause of genome instability in biological systems ranging from bacteria to mammals. Here we describe the genome-wide distribution of DNA:RNA hybrid prone loci in Saccharomyces cerevisiae by DNA:RNA immunoprecipitation (DRIP) followed by hybridization on tiling microarray. These profiles show that DNA:RNA hybrids preferentially accumulated at rDNA, Ty1 and Ty2 transposons, telomeric repeat regions and a subset of open reading frames (ORFs). The latter are generally highly transcribed and have high GC content. Interestingly, significant DNA:RNA hybrid enrichment was also detected at genes associated with antisense transcripts. The expression of antisense-associated genes was also significantly altered upon overexpression of RNase H, which degrades the RNA in hybrids. Finally, we uncover mutant-specific differences in the DRIP profiles of a Sen1 helicase mutant, RNase H deletion mutant and Hpr1 THO complex mutant compared to wild type, suggesting different roles for these proteins in DNA:RNA hybrid biology. Our profiles of DNA:RNA hybrid prone loci provide a resource for understanding the properties of hybrid-forming regions in vivo, extend our knowledge of hybrid-mitigating enzymes, and contribute to models of antisense-mediated gene regulation. A summary of this paper was presented at the 26th International Conference on Yeast Genetics and Molecular Biology, August 2013.

  15. Triage of oxidation-prone proteins by Sqstm1/p62 within the mitochondria

    SciTech Connect

    Lee, Minjung; Shin, Jaekyoon

    2011-09-16

    Highlights: {yields} The mitochondrion contains its own protein quality control system. {yields} p62 localizes within the mitochondria and forms mega-dalton sized complexes. {yields} p62 interacts with oxidation-prone proteins and the proteins of quality control. {yields} In vitro delivery of p62 improves mitochondrial functions. {yields} p62 is implicated as a participant in mitochondrial protein quality control. -- Abstract: As the mitochondrion is vulnerable to oxidative stress, cells have evolved several strategies to maintain mitochondrial integrity, including mitochondrial protein quality control mechanisms and autophagic removal of damaged mitochondria. Involvement of an autophagy adaptor, Sqstm1/p62, in the latter process has been recently described. In the present study, we provide evidence that a portion of p62 directly localizes within the mitochondria and supports stable electron transport by forming heterogeneous protein complexes. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) of mitochondrial proteins co-purified with p62 revealed that p62 interacts with several oxidation-prone proteins, including a few components of the electron transport chain complexes, as well as multiple chaperone molecules and redox regulatory enzymes. Accordingly, p62-deficient mitochondria exhibited compromised electron transport, and the compromised function was partially restored by in vitro delivery of p62. These results suggest that p62 plays an additional role in maintaining mitochondrial integrity at the vicinity of target machineries through its function in relation to protein quality control.

  16. Absence of food alternatives promotes risk-prone feeding of unpalatable substances in honey bees.

    PubMed

    Desmedt, Lucie; Hotier, Lucie; Giurfa, Martin; Velarde, Rodrigo; de Brito Sanchez, Maria Gabriela

    2016-08-18

    The question of why animals sometimes ingest noxious substances is crucial to understand unknown determinants of feeding behaviour. Research on risk-prone feeding behaviour has largely focused on energy budgets as animals with low energy budgets tend to ingest more aversive substances. A less explored possibility is that risk-prone feeding arises from the absence of alternative feeding options, irrespectively of energy budgets. Here we contrasted these two hypotheses in late-fall and winter honey bees. We determined the toxicity of various feeding treatments and showed that when bees can choose between sucrose solution and a mixture of this sucrose solution and a noxious/unpalatable substance, they prefer the pure sucrose solution and reject the mixtures, irrespective of their energy budget. Yet, when bees were presented with a single feeding option and their escape possibilities were reduced, they consumed unexpectedly some of the previously rejected mixtures, independently of their energy budget. These findings are interpreted as a case of feeding helplessness, in which bees behave as if it were utterly helpless to avoid the potentially noxious food and consume it. They suggest that depriving bees of variable natural food sources may have the undesired consequence of increasing their acceptance of food that would be otherwise rejected.

  17. The challenges of trafficking hydrolysis prone metals and ascidians as an archetype.

    PubMed

    Gaffney, Jean P; Valentine, Ann M

    2011-06-14

    Some of the metal ions that are required, exploited, or simply managed in biological systems are susceptible to hydrolysis and to hydrolytic precipitation in the aqueous, aerobic environment of much of biology. Organisms have evolved exquisite mechanisms for handling these metal ions, offering striking examples of biological control over inorganic coordination chemistry. This year marks the one hundredth anniversary of the discovery of remarkably high vanadium concentrations in the blood cells of the ascidian. In the ensuing years, these marine invertebrates were established as masters of the biological chemistry of very hydrolysis-prone metals, with various ascidian species accumulating high concentrations of iron, vanadium, and titanium, among others. These three metals have very different histories of biological relevance, and many questions remain about how, and ultimately why, these organisms sequester them. This Perspective addresses the aqueous coordination chemistry that organisms like ascidians must control if they are to manipulate hydrolysis-prone metal ions, and describes some of the ascidian biomolecules that have been implicated in this phenomenon. The recently available genome sequence for one ascidian species offers a glimpse into its metal-management arsenal. It offers the opportunity to map the relatively well-studied paradigm of iron management onto the genome of an organism that is intermediate in evolution between invertebrates and vertebrates. The ascidians have much to teach us about how to manage metals like iron, titanium, and vanadium and how that ability evolved.

  18. Greater trochanter location measurement using a three-dimensional motion capture system during prone hip extension

    PubMed Central

    Yu, Ji-Su; Oh, Jae-Seop

    2017-01-01

    [Purpose] The greater trochanter (GT) is an important structure in biomedical research, but the measurement methods require development. This study presents data from a new measurement method that does not use GT-marker-based measurement (No GT-m) in comparison with GT-marker based measurement (GT-m). [Subjects and Methods] We recruited 20 healthy subjects, who were asked to perform and maintain a prone position and then move to the prone hip extension. A motion capture system collected the kinematic data and the location of the GT was calculated by two measurements. [Results] GT migration distance differed significantly between the two measurements and the coefficient of the variation value was lower for the No GT-m method. Thigh lengths of the No GT-m method were comparable to the original lengths. There were significant differences between the GT-m and the other methods. [Conclusions] These data suggest that the GT-m method yielded a lower precision with a smaller GT migration distance. In the comparison of thigh length, the No GT-m method was in close agreement with the original length. We suggest that determining the location of the GT using the No GT-m has greater accuracy than the GT-m method. PMID:28265151

  19. Use of thermal inertia determined by HCMM to predict nocturnal cold prone areas in Florida

    NASA Technical Reports Server (NTRS)

    Allen, L. H., Jr. (Principal Investigator)

    1983-01-01

    Pairs of HCMM day-night thermal infrared (IR) data were selected during the 1978-79 winter to examine patterns of surface temperature and thermal inertia (TI) of peninsular Florida. The GOES and NOAA-6 thermal IR, as well as National Climatic Center temperatures and rainfall, were also used. The HCMM apparent thermal inertia (ATI) images closely corresponded to the general soil map of Florida, based on soil drainage classes. Areas with low ATI overlay well-drained soils, such as deep sands and drained organic soils, whereas with high ATI overlay areas with wetlands and bodies of water. The HCMM ATI images also corresponded well with GOES-detected winter nocturnal cold-prone areas. Use of HCMM data with Carlson's energy balance model showed both high moisture availability (MA) and high thermal inertia (TI) of wetland-type surfaces and low MA and low TI of upland, well-drained soils. Since soil areas with low TI develop higher temperatures during the day, then antecedent patterns of highest maximum daytime surface temperature can also be used to predict nocturnal cold-prone areas in Florida.

  20. Hydrological and hydraulic models for determination of flood-prone and flood inundation areas

    NASA Astrophysics Data System (ADS)

    Aksoy, Hafzullah; Sadan Ozgur Kirca, Veysel; Burgan, Halil Ibrahim; Kellecioglu, Dorukhan

    2016-05-01

    Geographic Information Systems (GIS) are widely used in most studies on water resources. Especially, when the topography and geomorphology of study area are considered, GIS can ease the work load. Detailed data should be used in this kind of studies. Because of, either the complication of the models or the requirement of highly detailed data, model outputs can be obtained fast only with a good optimization. The aim in this study, firstly, is to determine flood-prone areas in a watershed by using a hydrological model considering two wetness indexes; the topographical wetness index, and the SAGA (System for Automated Geoscientific Analyses) wetness index. The wetness indexes were obtained in the Quantum GIS (QGIS) software by using the Digital Elevation Model of the study area. Flood-prone areas are determined by considering the wetness index maps of the watershed. As the second stage of this study, a hydraulic model, HEC-RAS, was executed to determine flood inundation areas under different return period-flood events. River network cross-sections required for this study were derived from highly detailed digital elevation models by QGIS. Also river hydraulic parameters were used in the hydraulic model. Modelling technology used in this study is made of freely available open source softwares. Based on case studies performed on watersheds in Turkey, it is concluded that results of such studies can be used for taking precaution measures against life and monetary losses due to floods in urban areas particularly.

  1. Absence of food alternatives promotes risk-prone feeding of unpalatable substances in honey bees

    PubMed Central

    Desmedt, Lucie; Hotier, Lucie; Giurfa, Martin; Velarde, Rodrigo; de Brito Sanchez, Maria Gabriela

    2016-01-01

    The question of why animals sometimes ingest noxious substances is crucial to understand unknown determinants of feeding behaviour. Research on risk-prone feeding behaviour has largely focused on energy budgets as animals with low energy budgets tend to ingest more aversive substances. A less explored possibility is that risk-prone feeding arises from the absence of alternative feeding options, irrespectively of energy budgets. Here we contrasted these two hypotheses in late-fall and winter honey bees. We determined the toxicity of various feeding treatments and showed that when bees can choose between sucrose solution and a mixture of this sucrose solution and a noxious/unpalatable substance, they prefer the pure sucrose solution and reject the mixtures, irrespective of their energy budget. Yet, when bees were presented with a single feeding option and their escape possibilities were reduced, they consumed unexpectedly some of the previously rejected mixtures, independently of their energy budget. These findings are interpreted as a case of feeding helplessness, in which bees behave as if it were utterly helpless to avoid the potentially noxious food and consume it. They suggest that depriving bees of variable natural food sources may have the undesired consequence of increasing their acceptance of food that would be otherwise rejected. PMID:27534586

  2. An Analysis of Muscle Activities of Healthy Women during Pilates Exercises in a Prone Position.

    PubMed

    Kim, Bo-In; Jung, Ju-Hyeon; Shim, Jemyung; Kwon, Hae-Yeon; Kim, Haroo

    2014-01-01

    [Purpose] This study analyzed the activities of the back and hip muscles during Pilates exercises conducted in a prone position. [Subjects] The subjects were 18 healthy women volunteers who had practiced at a Pilates center for more than three months. [Methods] The subjects performed three Pilates exercises. To examine muscle activity during the exercises, 8-channel surface electromyography (Noraxon USA, Inc., Scottsdale, AZ) was used. The surface electrodes were attached to the bilateral latissimus dorsi muscle, multifidus muscle, gluteus maximus, and semitendinous muscle. Three Pilates back exercises were compared: (1) double leg kick (DLK), (2) swimming (SW), and (3) leg beat (LB). Electrical muscle activation was normalized to maximal voluntary isometric contraction. Repeated measures analysis of variance was performed to assess the differences in activation levels among the exercises. [Results] The activity of the multifidus muscle was significantly high for the SW (52.3±11.0, 50.9±9.8) and LB exercises(51.8±12.8, 48.3±13.9) and the activity of the semitendinosus muscle was higher for the LB exercise (49.2±8.7, 52.9±9.3) than for the DLK and SW exercises. [Conclusion] These results may provide basic material for when Pilates exercises are performed in a prone position and may be useful information on clinical Pilates for rehabilitation programs.

  3. Safe Sedation and Hypnosis using Dexmedetomidine for Minimally Invasive Spine Surgery in a Prone Position

    PubMed Central

    2014-01-01

    Dexmedetomidine, an imidazoline compound, is a highly selective α2-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties. In order to minimize the patients' pain and anxiety during minimally invasive spine surgery (MISS) when compared to conventional surgery under general anesthesia, an adequate conscious sedation (CS) or monitored anesthetic care (MAC) should be provided. Commonly used intravenous sedatives and hypnotics, such as midazolam and propofol, are not suitable for operations in a prone position due to undesired respiratory depression. Dexmedetomidine converges on an endogenous non-rapid eye movement (NREM) sleep-promoting pathway to exert its sedative effects. The great merit of dexmedetomidine for CS or MAC is the ability of the operator to recognize nerve damage during percutaneous endoscopic lumbar discectomy, a representative MISS. However, there are 2 shortcomings for dexmedetomidine in MISS: hypotension/bradycardia and delayed emergence. Its hypotension/bradycardiac effects can be prevented by ketamine intraoperatively. Using atipamezole (an α2-adrenoceptor antagonist) might allow doctors to control the rate of recovery from procedural sedation in the future. MAC, with other analgesics such as ketorolac and opioids, creates ideal conditions for MISS. In conclusion, dexmedetomidine provides a favorable surgical condition in patients receiving MISS in a prone position due to its unique properties of conscious sedation followed by unconscious hypnosis with analgesia. However, no respiratory depression occurs based on the dexmedetomidine-related endogenous sleep pathways involves the inhibition of the locus coeruleus in the pons, which facilitates VLPO firing in the anterior hypothalamus. PMID:25317279

  4. Thoracoscopic long myotomy in the prone position to treat rapid esophageal contractions with normal latency.

    PubMed

    Nomura, Tsutomu; Iwakiri, Katsuhiko; Matsutani, Takeshi; Hagiwara, Nobutoshi; Fujita, Itsuro; Nakamura, Yoshiharu; Kawami, Noriyuki; Miyashita, Masao; Uchida, Eiji

    2015-04-01

    A 56-year-old woman with an 8-year history of dysphagia and chest pain received a diagnosis of diffuse esophageal spasm by esophageal high-resolution manometry (HRM). Approximately 2 years of medical therapy was ineffective, and the patient's symptoms were worsening. Therefore, surgery was considered to be the most optimal treatment for this patient. The right thoracoscopic approach was selected because a long myotomy from the distal to proximal level of the esophagus was needed based on the HRM findings. The operation was performed in the prone position with establishment of pneumothorax. The total length of the myotomy was 16 cm, and the operation was finished within 2 hours. After the operation, the symptoms were considerably improved and no contractions were detected by HRM. The HRM findings before the operation were classified as rapid contractions with normal latency based on the 2012 Chicago classification of esophageal motility. Treatment for patients with rapid esophageal contractions with normal latency has not been previously described; however, treatment for diffuse esophageal spasm was considered to be pertinent to this patient. In conclusion, right thoracoscopic esophageal long myotomy in the prone position with establishment of pneumothorax may be useful when a proximal-level esophagomyotomy is required based on preoperative mapping by HRM.

  5. Functioning of Neural Systems Supporting Emotion Regulation in Anxiety-Prone Individuals

    PubMed Central

    Campbell-Sills, Laura; Simmons, Alan N.; Lovero, Kathryn L.; Rochlin, Alexis A.; Paulus, Martin P.; Stein, Murray B.

    2010-01-01

    Previous neuroimaging studies suggest that prefrontal cortex (PFC) modulation of the amygdala and related limbic structures is an underlying neural substrate of effortful emotion regulation. Anxiety-prone individuals experience excessive negative emotions, signaling potential dysfunction of systems supporting down-regulation of negative emotions. We examined the hypothesis that anxious individuals require increased recruitment of lateral and medial PFC to decrease negative emotions. An emotion regulation task that involved viewing moderately negative images was presented during functional magnetic resonance imaging (fMRI). Participants with elevated trait anxiety scores (n = 13) and normal trait anxiety scores (n = 13) were trained to reduce negative emotions using cognitive reappraisal. Blood oxygenation level-dependent (BOLD) changes were contrasted for periods when participants were reducing emotions versus when they were maintaining emotions. Compared to healthy controls, anxious participants showed greater activation of brain regions implicated in effortful (lateral PFC) and automatic (subgenual anterior cingulate cortex) control of emotions during down-regulation of negative emotions. Left ventrolateral PFC activity was associated with greater self-reported reduction of distress in anxious participants, but not in healthy controls. These findings provide evidence of altered functioning of neural substrates of emotion regulation in anxiety-prone individuals. Anxious participants required greater engagement of lateral and medial PFC in order to successfully reduce negative emotions. PMID:20673804

  6. Optical measurement of dimensional parameters of the breast with subjects in prone position

    PubMed Central

    Roessler, Ann-Christin; Althoff, Felix; Jaeger, Florian; Kalender, Willi; Wenkel, Evelyn

    2015-01-01

    Abstract. Various applications require information on breast parameters, such as breast length and volume. An optical system was designed and tested for measuring these parameters with subjects in a prone position. The study results were used for optimizing patient positioning and handling for a future breast computed tomography (BCT) system. Measurements were conducted using an optical measurement system. To test the functionality and accuracy of the system, measurements were performed using reference phantoms. Additionally, 20 women and 5 men were examined to calculate breast parameters in alternative positions and breathing states. The results of the optical measurements were compared with magnetic resonance imaging (MRI) measurements. Volume and length of the reference phantoms were determined with errors below 2%. The patient study demonstrated a mean breast volume of 530.7 ml for women during normal breathing. During an exhalation state, breast volume increased significantly by 17.7 ml in comparison with normal breathing. Differences with MRI measurements were found to be 3% for breast length and 9% for breast volume on average. The proposed optical measurement system was found to be suitable for measuring the dimensional parameters of the breast in a prone position and provides a tool for evaluating breast coverage for BCT. PMID:26240833

  7. Seismic hazard assessment and pattern recognition of earthquake prone areas in the Po Plain (Italy)

    NASA Astrophysics Data System (ADS)

    Gorshkov, Alexander; Peresan, Antonella; Soloviev, Alexander; Panza, Giuliano F.

    2014-05-01

    A systematic and quantitative assessment, capable of providing first-order consistent information about the sites where large earthquakes may occur, is crucial for the knowledgeable seismic hazard evaluation. The methodology for the pattern recognition of areas prone to large earthquakes is based on the morphostructural zoning method (MSZ), which employs topographic data and present-day tectonic structures for the mapping of earthquake-controlling structures (i.e. the nodes formed around lineaments intersections) and does not require the knowledge about past seismicity. The nodes are assumed to be characterized by a uniform set of topographic, geologic, and geophysical parameters; on the basis of such parameters the pattern recognition algorithm defines a classification rule to discriminate seismogenic and non-seismogenic nodes. This methodology has been successfully applied since the early 1970s in a number of regions worldwide, including California, where it permitted the identification of areas that have been subsequently struck by strong events and that previously were not considered prone to strong earthquakes. Recent studies on the Iberian Peninsula and the Rhone Valley, have demonstrated the applicability of MSZ to flat basins, with a relatively flat topography. In this study, the analysis is applied to the Po Plain (Northern Italy), an area characterized by a flat topography, to allow for the systematic identification of the nodes prone to earthquakes with magnitude larger or equal to M=5.0. The MSZ method differs from the standard morphostructural analysis where the term "lineament" is used to define the complex of alignments detectable on topographic maps or on satellite images. According to that definition the lineament is locally defined and the existence of the lineament does not depend on the surrounding areas. In MSZ, the primary element is the block - a relatively homogeneous area - while the lineament is a secondary element of the morphostructure

  8. Review of ion accelerators

    SciTech Connect

    Alonso, J.

    1990-06-01

    The field of ion acceleration to higher energies has grown rapidly in the last years. Many new facilities as well as substantial upgrades of existing facilities have extended the mass and energy range of available beams. Perhaps more significant for the long-term development of the field has been the expansion in the applications of these beams, and the building of facilities dedicated to areas outside of nuclear physics. This review will cover many of these new developments. Emphasis will be placed on accelerators with final energies above 50 MeV/amu. Facilities such as superconducting cyclotrons and storage rings are adequately covered in other review papers, and so will not be covered here.

  9. Accelerator research studies

    SciTech Connect

    Not Available

    1992-01-01

    The Accelerator Research Studies program at the University of Maryland, sponsored by the Department of Energy under grant number DE-FG05-91ER40642, is currently in the first year of a three-year funding cycle. The program consists of the following three tasks: TASK A, Study of Transport and Longitudinal Compression of Intense, High-Brightness Beams, TASK B, Study of Collective Ion Acceleration by Intense Electron Beams and Pseudospark Produced High Brightness Electron Beams; TASK C, Study of a Gyroklystron High-power Microwave Source for Linear Colliders. In this report we document the progress that has been made during the past year for each of the three tasks.

  10. Commissioning the GTA accelerator

    SciTech Connect

    Sander, O.R.; Atkins, W.H.; Bolme, G.O.; Bowling, S.; Brown, S.; Cole, R.; Gilpatrick, J.D.; Garnett, R.; Guy, F.W.; Ingalls, W.B.; Johnson, K.F.; Kerstiens, D.; Little, C.; Lohsen, R.A.; Lloyd, S.; Lysenko, W.P.; Mottershead, C.T.; Neuschaefer, G.; Power, J.; Rusthoi, D.P.; Sandoval, D.P. Stevens, R.R. Jr.; Vaughn, G.; Wadlinger, E.A.; Yuan, V.; Connolly, R.; Weiss, R.; Saadatmand, K.

    1992-09-01

    The Ground Test Accelerator (GTA) is supported by the Strategic Defense command as part of their Neutral Particle Beam (NPB) program. Neutral particles have the advantage that in space they are unaffected by the earth`s magnetic field and travel in straight lines unless they enter the earth`s atmosphere and become charged by stripping. Heavy particles are difficult to stop and can probe the interior of space vehicles; hence, NPB can function as a discriminator between warheads and decoys. We are using GTA to resolve the physics and engineering issues related to accelerating, focusing, and steering a high-brightness, high-current H{sup -} beam and then neutralizing it. Our immediate goal is to produce a 24-MeV, 50mA device with a 2% duty factor.

  11. Commissioning the GTA accelerator

    SciTech Connect

    Sander, O.R.; Atkins, W.H.; Bolme, G.O.; Bowling, S.; Brown, S.; Cole, R.; Gilpatrick, J.D.; Garnett, R.; Guy, F.W.; Ingalls, W.B.; Johnson, K.F.; Kerstiens, D.; Little, C.; Lohsen, R.A.; Lloyd, S.; Lysenko, W.P.; Mottershead, C.T.; Neuschaefer, G.; Power, J.; Rusthoi, D.P.; Sandoval, D.P. Stevens, R.R. Jr.; Vaughn, G.; Wadlinger, E.A.; Yuan, V. ); Connolly, R.; Weiss, R. (Gr

    1992-01-01

    The Ground Test Accelerator (GTA) is supported by the Strategic Defense command as part of their Neutral Particle Beam (NPB) program. Neutral particles have the advantage that in space they are unaffected by the earth's magnetic field and travel in straight lines unless they enter the earth's atmosphere and become charged by stripping. Heavy particles are difficult to stop and can probe the interior of space vehicles; hence, NPB can function as a discriminator between warheads and decoys. We are using GTA to resolve the physics and engineering issues related to accelerating, focusing, and steering a high-brightness, high-current H{sup -} beam and then neutralizing it. Our immediate goal is to produce a 24-MeV, 50mA device with a 2% duty factor.

  12. Auroral ion acceleration

    NASA Astrophysics Data System (ADS)

    Shalimov, S. L.

    From the altitude of 500 km to 15 R sub E everywhere conic like distributions of H+, O+, He+ ions are moving upwards from the ionosphere along the geomagnetic field lines in the auroral zone. The distributed ions suggest the existence of ion transverse acceleration mechanisms (ITAM) acting below the observation point. The more plausible mechanisms are connected with the resonance of the type wave particle between ions and the observed EIC and LH waves and are also due to the existence of the local transverse electric fields in the ionoshere and the magnetosphere. The known ion transverse acceleration mechanisms were complemented by new results. The conical distributions of ionospheric ions at different altitudes in the auroral zone are pointed out.

  13. Review of accelerator instrumentation

    SciTech Connect

    Pellegrin, J.L.

    1980-05-01

    Some of the problems associated with the monitoring of accelerator beams, particularly storage rings' beams, are reviewed along with their most common solutions. The various electrode structures used for the measurement of beam current, beam position, and the detection of the bunches' transverse oscillations, yield pulses with sub-nanosecond widths. The electronics for the processing of these short pulses involves wide band techniques and circuits usually not readily available from industry or the integrated circuit market: passive or active, successive integrations, linear gating, sample-and-hold circuits with nanosecond acquisition time, etc. This report also presents the work performed recently for monitoring the ultrashort beams of colliding linear accelerators or single-pass colliders. To minimize the beam emittance, the beam position must be measured with a high resolution, and digitized on a pulse-to-pulse basis. Experimental results obtained with the Stanford two-mile Linac single bunches are included.

  14. Hardware Accelerated Simulated Radiography

    SciTech Connect

    Laney, D; Callahan, S; Max, N; Silva, C; Langer, S; Frank, R

    2005-04-12

    We present the application of hardware accelerated volume rendering algorithms to the simulation of radiographs as an aid to scientists designing experiments, validating simulation codes, and understanding experimental data. The techniques presented take advantage of 32 bit floating point texture capabilities to obtain validated solutions to the radiative transport equation for X-rays. An unsorted hexahedron projection algorithm is presented for curvilinear hexahedra that produces simulated radiographs in the absorption-only regime. A sorted tetrahedral projection algorithm is presented that simulates radiographs of emissive materials. We apply the tetrahedral projection algorithm to the simulation of experimental diagnostics for inertial confinement fusion experiments on a laser at the University of Rochester. We show that the hardware accelerated solution is faster than the current technique used by scientists.

  15. Adaptive control for accelerators

    DOEpatents

    Eaton, Lawrie E.; Jachim, Stephen P.; Natter, Eckard F.

    1991-01-01

    An adaptive feedforward control loop is provided to stabilize accelerator beam loading of the radio frequency field in an accelerator cavity during successive pulses of the beam into the cavity. A digital signal processor enables an adaptive algorithm to generate a feedforward error correcting signal functionally determined by the feedback error obtained by a beam pulse loading the cavity after the previous correcting signal was applied to the cavity. Each cavity feedforward correcting signal is successively stored in the digital processor and modified by the feedback error resulting from its application to generate the next feedforward error correcting signal. A feedforward error correcting signal is generated by the digital processor in advance of the beam pulse to enable a composite correcting signal and the beam pulse to arrive concurrently at the cavity.

  16. Pulsed electromagnetic gas acceleration

    NASA Technical Reports Server (NTRS)

    Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

    1971-01-01

    Experimental data were combined with one-dimensional conservation relations to yield information on the energy deposition ratio in a parallel-plate accelerator, where the downstream flow was confined to a constant area channel. Approximately 70% of the total input power was detected in the exhaust flow, of which only about 20% appeared as directed kinetic energy, thus implying that a downstream expansion to convert chamber enthalpy into kinetic energy must be an important aspect of conventional high power MPD arcs. Spectroscopic experiments on a quasi-steady MPD argon accelerator verified the presence of A(III) and the absence of A(I), and indicated an azimuthal structure in the jet related to the mass injection locations. Measurements of pressure in the arc chamber and impact pressure in the exhaust jet using a piezocrystal backed by a Plexiglas rod were in good agreement with the electromagnetic thrust model.

  17. Pulsed Drift Tube Accelerator

    SciTech Connect

    Faltens, A.

    2004-10-25

    The pulsed drift-tube accelerator (DTA) concept was revived by Joe Kwan and John Staples and is being considered for the HEDP/WDM application. It could be used to reach the full energy or as an intermediate accelerator between the diode and a high gradient accelerator such as multi-beam r.f. In the earliest LBNL HIF proposals and conceptual drivers it was used as an extended injector to reach energies where an induction linac with magnetic quadrupoles is the best choice. For HEDP, because of the very short pulse duration, the DTA could provide an acceleration rate of about 1MV/m. This note is divided into two parts: the first, a design based on existing experience; the second, an optimistic extrapolation. The first accelerates 16 parallel K{sup +} beams at a constant line charge density of 0.25{micro} C/m per beam to 10 MeV; the second uses a stripper and charge selector at around 4MeV followed by further acceleration to reach 40 MeV. Both benefit from more compact sources than the present 2MV injector source, although that beam is the basis of the first design and is a viable option. A pulsed drift-tube accelerator was the first major HIF experiment at LBNL. It was designed to produce a 2{micro}s rectangular 1 Ampere C{sub s}{sup +} beam at 2MeV. It ran comfortably at 1.6MeV for several years, then at lower voltages and currents for other experiments, and remnants of that experiment are in use in present experiments, still running 25 years later. The 1A current, completely equivalent to 1.8A K{sup +}, was chosen to be intermediate between the beamlets appropriate for a multi-beam accelerator, and a single beam of, say, 10A, at injection energies. The original driver scenarios using one large beam on each side of the reactor rapidly fell out of favor because of the very high transverse and longitudinal fields from the beam space charge, circa 1MV/cm and 250 kV/cm respectively, near the chamber and because of aberrations in focusing a large diameter beam down to a 1

  18. SUPERDIFFUSIVE SHOCK ACCELERATION

    SciTech Connect

    Perri, S.; Zimbardo, G.

    2012-05-10

    The theory of diffusive shock acceleration is extended to the case of superdiffusive transport, i.e., when the mean square deviation grows proportionally to t{sup {alpha}}, with {alpha} > 1. Superdiffusion can be described by a statistical process called Levy random walk, in which the propagator is not a Gaussian but it exhibits power-law tails. By using the propagator appropriate for Levy random walk, it is found that the indices of energy spectra of particles are harder than those obtained where a normal diffusion is envisaged, with the spectral index decreasing with the increase of {alpha}. A new scaling for the acceleration time is also found, allowing substantially shorter times than in the case of normal diffusion. Within this framework we can explain a number of observations of flat spectra in various astrophysical and heliospheric contexts, for instance, for the Crab Nebula and the termination shock of the solar wind.

  19. Accelerators for Cancer Therapy

    DOE R&D Accomplishments Database

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  20. Differences in Irradiated Lung Gene Transcription Between Fibrosis-Prone C57BL/6NHsd and Fibrosis-Resistant C3H/HeNHsd Mice

    PubMed Central

    Kalash, Ronny; Berhane, Hebist; Au, Jeremiah; Rhieu, Byung Han; Epperly, Michael W.; Goff, Julie; Dixon, Tracy; Wang, Hong; Zhang, Xichen; Franicola, Darcy; Shinde, Ashwin; Greenberger, Joel S.

    2014-01-01

    Background/Aim We compared pulmonary irradiation-induced whole lung, gene transcripts, over 200 days after 20 Gy thoracic irradiation in fibrosis-prone C57BL/6NHsd with fibrosis-resistant C3H/HeNHsd female mice. Materials and Methods Lung specimens were analyzed by rt-PCR and changes over time in representative gene transcript levels were correlated with protein levels using Western Blot. Results C3H/HeNHsd mice showed a significantly longer duration of elevation of gene transcripts for stress-response genes (NFkβ, Nrf2, Sp1, Ap1), radioprotection gene (SOD2), and endothelial cell associated genes (vWF, VEGFa). C57BL/6NHsd mice showed acute elevation then downregulation and a second elevation in gene transcripts for NFkβ, CTGF, IGFbp7, TNFα, collagen1a, and TLR4. There were reciprocal patterns of elevation and decrease in levels of transcripts for epigenetic reader proteins Brd1, 2, 3, and 4 between mouse strains. Conclusions Regulatory pathways linked to radiation pulmonary fibrosis may identify new targets for anti-fibrotic radiation mitigators. PMID:24632969

  1. Chronic pain and impaired glial glutamate transporter function in lupus-prone mice are ameliorated by blocking macrophage colony-stimulating factor-1 receptors.

    PubMed

    Yan, Xisheng; Maixner, Dylan W; Li, Fen; Weng, Han-Rong

    2017-03-01

    Systemic lupus erythematosus (SLE) is a multi-organ disease of unknown etiology in which the normal immune responses are directed against the body's own healthy tissues. Patients with SLE often suffer from chronic pain. Currently, no animal studies have been reported about the mechanisms underlying pain in SLE. In this study, the development of chronic pain in MRL lupus-prone (MRL/lpr) mice, a well-established lupus mouse model, was characterized for the first time. We found that female MRL/lpr mice developed thermal hyperalgesia at the age of 13 weeks, and mechanical allodynia at the age of 16 weeks. MRL/lpr mice with chronic pain had activation of microglia and astrocytes, over-expression of macrophage colony-stimulating factor-1 (CSF-1) and interleukin-1 beta (IL-1β), as well as suppression of glial glutamate transport function in the spinal cord. Intrathecal injection of either the CSF-1 blocker or IL-1 inhibitor attenuated thermal hyperalgesia in MRL/lpr mice. We provide evidence that the suppressed activity of glial glutamate transporters in the spinal dorsal horn in MRL/lpr mice is caused by activation of the CSF-1 and IL-1β signaling pathways. Our findings suggest that targeting the CSF-1 and IL-1β signaling pathways or the glial glutamate transporter in the spinal cord is an effective approach for the management of chronic pain caused by SLE.

  2. Accelerated plate tectonics.

    PubMed

    Anderson, D L

    1975-03-21

    The concept of a stressed elastic lithospheric plate riding on a viscous asthenosphere is used to calculate the recurrence interval of great earthquakes at convergent plate boundaries, the separation of decoupling and lithospheric earthquakes, and the migration pattern of large earthquakes along an arc. It is proposed that plate motions accelerate after great decoupling earthquakes and that most of the observed plate motions occur during short periods of time, separated by periods of relative quiescence.

  3. Linear induction accelerator

    DOEpatents

    Buttram, M.T.; Ginn, J.W.

    1988-06-21

    A linear induction accelerator includes a plurality of adder cavities arranged in a series and provided in a structure which is evacuated so that a vacuum inductance is provided between each adder cavity and the structure. An energy storage system for the adder cavities includes a pulsed current source and a respective plurality of bipolar converting networks connected thereto. The bipolar high-voltage, high-repetition-rate square pulse train sets and resets the cavities. 4 figs.

  4. Compact pulsed accelerator

    SciTech Connect

    Rhee, M.J.; Schneider, R.F.

    1983-01-01

    The formation of fast pulses from a current charged transmission line and opening switch is described. By employing a plasma focus as an opening switch and diode in the prototype device, a proton beam of peak energy 250 keV is produced. The time integrated energy spectrum of the beam is constructed from a Thomson spectrograph. Applications of this device as an inexpensive and portable charged particle accelerator are discussed. 7 refs., 5 figs., 1 tab.

  5. ION ACCELERATION SYSTEM

    DOEpatents

    Luce, J.S.; Martin, J.A.

    1960-02-23

    Well focused, intense ion beams are obtained by providing a multi- apertured source grid in front of an ion source chamber and an accelerating multi- apertured grid closely spaced from and in alignment with the source grid. The longest dimensions of the elongated apertures in the grids are normal to the direction of the magnetic field used with the device. Large ion currents may be withdrawn from the source, since they do not pass through any small focal region between the grids.

  6. Frontiers of accelerator instrumentation

    SciTech Connect

    Ross, M.

    1992-08-01

    New technology has permitted significant performance improvements of established instrumentation techniques including beam position and profile monitoring. Fundamentally new profile monitor strategies are required for the next generation of accelerators, especially linear colliders (LC). Beams in these machines may be three orders of magnitude smaller than typical beams in present colliders. In this paper we review both the present performance levels achieved by conventional systems and present some new ideas for future colliders.

  7. Accelerator simulation using computers

    SciTech Connect

    Lee, M.; Zambre, Y.; Corbett, W.

    1992-01-01

    Every accelerator or storage ring system consists of a charged particle beam propagating through a beam line. Although a number of computer programs exits that simulate the propagation of a beam in a given beam line, only a few provide the capabilities for designing, commissioning and operating the beam line. This paper shows how a multi-track'' simulation and analysis code can be used for these applications.

  8. Accelerator simulation using computers

    SciTech Connect

    Lee, M.; Zambre, Y.; Corbett, W.

    1992-01-01

    Every accelerator or storage ring system consists of a charged particle beam propagating through a beam line. Although a number of computer programs exits that simulate the propagation of a beam in a given beam line, only a few provide the capabilities for designing, commissioning and operating the beam line. This paper shows how a ``multi-track`` simulation and analysis code can be used for these applications.

  9. Accelerated Profile HMM Searches.

    PubMed

    Eddy, Sean R

    2011-10-01

    Profile hidden Markov models (profile HMMs) and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the "multiple segment Viterbi" (MSV) algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call "sparse rescaling". These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches.

  10. Acceleration during magnetic reconnection

    SciTech Connect

    Beresnyak, Andrey; Li, Hui

    2015-07-16

    The presentation begins with colorful depictions of solar x-ray flares and references to pulsar phenomena. Plasma reconnection is complex, could be x-point dominated or turbulent, field lines could break due to either resistivity or non-ideal effects, such as electron pressure anisotropy. Electron acceleration is sometimes observed, and sometimes not. One way to study this complex problem is to have many examples of the process (reconnection) and compare them; the other way is to simplify and come to something robust. Ideal MHD (E=0) turbulence driven by magnetic energy is assumed, and the first-order acceleration is sought. It is found that dissipation in big (length >100 ion skin depths) current sheets is universal and independent on microscopic resistivity and the mean imposed field; particles are regularly accelerated while experiencing curvature drift in flows driven by magnetic tension. One example of such flow is spontaneous reconnection. This explains hot electrons with a power-law tail in solar flares, as well as ultrashort time variability in some astrophysical sources.

  11. Accelerator mass spectrometry.

    PubMed

    Hellborg, Ragnar; Skog, Göran

    2008-01-01

    In this overview the technique of accelerator mass spectrometry (AMS) and its use are described. AMS is a highly sensitive method of counting atoms. It is used to detect very low concentrations of natural isotopic abundances (typically in the range between 10(-12) and 10(-16)) of both radionuclides and stable nuclides. The main advantages of AMS compared to conventional radiometric methods are the use of smaller samples (mg and even sub-mg size) and shorter measuring times (less than 1 hr). The equipment used for AMS is almost exclusively based on the electrostatic tandem accelerator, although some of the newest systems are based on a slightly different principle. Dedicated accelerators as well as older "nuclear physics machines" can be found in the 80 or so AMS laboratories in existence today. The most widely used isotope studied with AMS is 14C. Besides radiocarbon dating this isotope is used in climate studies, biomedicine applications and many other fields. More than 100,000 14C samples are measured per year. Other isotopes studied include 10Be, 26Al, 36Cl, 41Ca, 59Ni, 129I, U, and Pu. Although these measurements are important, the number of samples of these other isotopes measured each year is estimated to be less than 10% of the number of 14C samples.

  12. Electrostatic Plasma Accelerator (EPA)

    NASA Technical Reports Server (NTRS)

    Brophy, John R.; Aston, Graeme

    1995-01-01

    The application of electric propulsion to communications satellites, however, has been limited to the use of hydrazine thrusters with electric heaters for thrust and specific impulse augmentation. These electrothermal thrusters operate at specific impulse levels of approximately 300 s with heater powers of about 500 W. Low power arcjets (1-3 kW) are currently being investigated as a way to increase specific impulse levels to approximately 500 s. Ion propulsion systems can easily produce specific impulses of 3000 s or greater, but have yet to be applied to communications satellites. The reasons most often given for not using ion propulsion systems are their high level of overall complexity, low thrust with long burn times, and the difficulty of integrating the propulsion system into existing commercial spacecraft busses. The Electrostatic Plasma Accelerator (EPA) is a thruster concept which promises specific impulse levels between low power arcjets and those of the ion engine while retaining the relative simplicity of the arcjet. The EPA thruster produces thrust through the electrostatic acceleration of a moderately dense plasma. No accelerating electrodes are used and the specific impulse is a direct function of the applied discharge voltage and the propellant atomic mass.

  13. Berkeley Proton Linear Accelerator

    DOE R&D Accomplishments Database

    Alvarez, L. W.; Bradner, H.; Franck, J.; Gordon, H.; Gow, J. D.; Marshall, L. C.; Oppenheimer, F. F.; Panofsky, W. K. H.; Richman, C.; Woodyard, J. R.

    1953-10-13

    A linear accelerator, which increases the energy of protons from a 4 Mev Van de Graaff injector, to a final energy of 31.5 Mev, has been constructed. The accelerator consists of a cavity 40 feet long and 39 inches in diameter, excited at resonance in a longitudinal electric mode with a radio-frequency power of about 2.2 x 10{sup 6} watts peak at 202.5 mc. Acceleration is made possible by the introduction of 46 axial "drift tubes" into the cavity, which is designed such that the particles traverse the distance between the centers of successive tubes in one cycle of the r.f. power. The protons are longitudinally stable as in the synchrotron, and are stabilized transversely by the action of converging fields produced by focusing grids. The electrical cavity is constructed like an inverted airplane fuselage and is supported in a vacuum tank. Power is supplied by 9 high powered oscillators fed from a pulse generator of the artificial transmission line type.

  14. ACCELERATION INTEGRATING MEANS

    DOEpatents

    Wilkes, D.F.

    1961-08-29

    An acceleration responsive device is described. A housing has at one end normally open electrical contacts and contains a piston system with a first part of non-magnetic material having metering orifices in the side walls for forming an air bearing between it and the walls of the housing; this first piston part is normally held against the other end of the housing from the noted contacts by a second piston or reset part. The reset part is of partly magnetic material, is separable from the flrst piston part, and is positioned within the housing intermediate the contacts and the first piston part. A magnet carried by the housing imposes a retaining force upon the reset part, along with a helical compression spring that is between the reset part and the end with the contacts. When a predetermined acceleration level is attained, the reset part overcomes the bias or retaining force provided by the magnet and the spring'' snaps'' into a depression in the housing adjacent the contacts. The first piston part is then free to move toward the contacts with its movement responsive tc acceleration forces and the metering orifices. (AEC)

  15. French nuclear physics accelerator opens

    NASA Astrophysics Data System (ADS)

    Dumé, Belle

    2016-12-01

    A new €140m particle accelerator for nuclear physics located at the French Large Heavy Ion National Accelerator (GANIL) in Caen was inaugurated last month in a ceremony attended by French president François Hollande.

  16. Mouse bladder wall injection.

    PubMed

    Fu, Chi-Ling; Apelo, Charity A; Torres, Baldemar; Thai, Kim H; Hsieh, Michael H

    2011-07-12

    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

  17. Prone Positioning Causes the Heart To Be Displaced Anteriorly Within the Thorax: Implications for Breast Cancer Treatment

    SciTech Connect

    Chino, Junzo P. Marks, Lawrence B.

    2008-03-01

    Introduction: Prone positioning has been suggested as an alternative to the conventional supine position for patients receiving breast radiotherapy, but few data exist on how this may alter heart location. We herein quantitatively compare the intrathoracic location of the heart in the prone and supine positions in patients treated for breast cancer. Methods and Materials: In 16 patients treated with tangent photons for breast cancer, the computed tomography planning images (obtained in the supine position) and diagnostic magnetic resonance images (obtained in the prone position) were studied. For each case, the distance between the anterior pericardium and the anterior chest wall was measured at nine specific points; three points at each of three axial levels. The differences in the measurements between the prone and supine positions were compared with the Wilcoxon signed-rank test. Results: There is a systematic displacement of the lateral and superior aspect of the heart closer to the chest wall in the prone vs. supine position (mean displacement 19 mm (95% confidence interval 13.7-25.1 mm, p < 0.001); the medial and inferior aspects remain fixed. There was also a reduction in volume of lung interposed between the heart and chest wall when prone (mean decrease of 22 mL, p < 0.001 for difference). Conclusions: The superior and lateral aspects of the heart typically move anteriorly during prone positioning compared with the supine position. This may have negative consequences in situations in which the high-risk target tissues include the chest wall or deep breast.

  18. Plasma accelerator experiments in Yugoslavia

    NASA Astrophysics Data System (ADS)

    Purić, J.; Astashynski, V. M.; Kuraica, M. M.; Dojčinovié, I. P.

    2002-12-01

    An overview is given of the results obtained in the Plasma Accelerator Experiments in Belgrade, using quasi-stationary high current plasma accelerators constructed within the framework of the Yugoslavia-Belarus Joint Project. So far, the following plasma accelerators have been realized: Magnetoplasma Compressor type (MPC); MPC Yu type; one stage Erosive Plasma Dynamic System (EPDS) and, in final stage of construction two stage Quasi-Stationary High Current Plasma Accelerator (QHPA).

  19. Science and Technology of Accelerators

    NASA Astrophysics Data System (ADS)

    Valerio Lizarraga, Cristhian; Castilla Loaeza, Alejandro; Guillermo Cantón, Gerardo; Duarte, Carlos; Chavez Valenzuela, Daniel; Hernández Chahín, Karim; Cuna, Humberto Maury; Medina Medrano, Luis; Reyes Herrera, Juan; Sosa Güitrón, Salvador; Valdivia García, Alan; Rendón, Bruce Yee

    2016-10-01

    The Mexican Particle Accelerator Community (CMAP) was created in 2015 and currently its members participate in different experiments around the world. Using their expertise, they are working in the development of the particle accelerators area in Mexico. This paper provides a summary of the research done by its members and presents the preliminary design of an electron linear particle accelerator (eLINAC). This proposal will be the first accelerator designed and created in Mexico.

  20. POT of gold: modeling dyskeratosis congenita in the mouse

    PubMed Central

    Autexier, Chantal

    2008-01-01

    Dyskeratosis congenita (DC) is a rare syndrome, characterized by cutaneous abnormalities and premature death caused by bone marrow failure. In this issue of Genes & Development, Hockemeyer and colleagues (pp. 1773–1785) report a new mouse model that reconstitutes key features of DC. Disease phenotypes are generated by a POT1b deletion in a telomerase-deficient background that accelerates the shortening of telomeres by degradation. PMID:18593874